Abstract
Background: Women with preeclampsia frequently have disorders of calcium metabolism during their pregnancies, including hypocalciuria and low vitamin D levels. The link between fetal sex and vitamin D and vitamin D binding protein levels in pregnancy and preeclampsia is not clear.
Aim: Present study was designed to explore sex-specific variations in vitamin D and vitamin D binding protein levels in maternal and umbilical cord blood samples for age and gestation matched 20 primigravida normotensive and 20 primigravida with preeclampsia with a singleton pregnancy.
Methods: Routine investigations, vitamin D binding protein (VDBP), and serum vitamin D in both maternal serum and cord blood were measured in both groups. Association between maternal and cord blood vitamin D levels was highly positive in both cases and control with babies of either sex.
Results: This association exhibited sexual dimorphism between cord blood vitamin D and vitamin D binding protein (VDBP) suggesting that the occurrence of pregnancy complications differs according to fetal sex with a higher cardiovascular and metabolic load for the mother in the presence of a male fetus.
Conclusion: Vitamin D binding protein (VDBP) measurement along with vitamin D level should be advised in clinical practice for early detection and screening.
Graphical Abstract
[1]
American College of Obstetricians and Gynecologists. Task force on hypertension in pregnancy. Obstet Gynecol 2013; 122(5): 1122-31.
[PMID: 24150027]
[PMID: 24150027]
[2]
Phipps E, Prasanna D, Brima W, Jim B. Preeclampsia Updates in pathogenesis, definitions and guidelines. Clin J Am Soc Nephrol 2016; 11(6): 1102-13.
[http://dx.doi.org/10.2215/CJN.12081115] [PMID: 27094609]
[http://dx.doi.org/10.2215/CJN.12081115] [PMID: 27094609]
[3]
Sajith M, Nimbargi V, Modi A, Sumariya R, Pawar A. Incidence of pregnancy induced hypertension and prescription pattern of antihypertensive drugs in pregnancy. Int J Pharm Sci Res 2014; 23: 163-70.
[4]
Dekker GA, Sibai BM. Etiology and pathogenesis of preeclampsia: Current concepts. Am J Obstet Gynecol 1998; 179(5): 1359-75.
[http://dx.doi.org/10.1016/S0002-9378(98)70160-7] [PMID: 9822529]
[http://dx.doi.org/10.1016/S0002-9378(98)70160-7] [PMID: 9822529]
[5]
Schuiling GA, Faas MM. Etiology and pathogenesis of preeclampsia: Current concepts. Am J Obstet Gynecol 1999; 181(4): 1036-7.
[http://dx.doi.org/10.1016/S0002-9378(99)70346-7] [PMID: 10521945]
[http://dx.doi.org/10.1016/S0002-9378(99)70346-7] [PMID: 10521945]
[6]
Hollis BW, Johnson D, Hulsey TC, Ebeling M, Wagner CL. Vitamin D supplementation during pregnancy: Double-blind, randomized clinical trial of safety and effectiveness. J Bone Miner Res 2011; 26(10): 2341-57.
[http://dx.doi.org/10.1002/jbmr.463] [PMID: 21706518]
[http://dx.doi.org/10.1002/jbmr.463] [PMID: 21706518]
[7]
Bikle DD, Gee E, Halloran B, Kowalski MA, Ryzen E, Haddad JG. Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein. J Clin Endocrinol Metab 1986; 63(4): 954-9.
[http://dx.doi.org/10.1210/jcem-63-4-954] [PMID: 3745408]
[http://dx.doi.org/10.1210/jcem-63-4-954] [PMID: 3745408]
[8]
Wagner CL, Taylor SN, Johnson DD, Hollis BW. The role of vitamin D in pregnancy and lactation: Emerging concepts. Womens Health (Lond Engl) 2012; 8(3): 323-40.
[http://dx.doi.org/10.2217/WHE.12.17] [PMID: 22554179]
[http://dx.doi.org/10.2217/WHE.12.17] [PMID: 22554179]
[9]
Walker VP, Zhang X, Rastegar I, et al. Cord blood vitamin D status impacts innate immune responses. J Clin Endocrinol Metab 2011; 96(6): 1835-43.
[http://dx.doi.org/10.1210/jc.2010-1559] [PMID: 21470993]
[http://dx.doi.org/10.1210/jc.2010-1559] [PMID: 21470993]
[10]
Bouillon R, Van Assche FA, Van Baelen H, Heyns W, DeMoor P. Influence of the vitamin D-binding protein on serum concentrations of 1,25(OH)2D. J Clin Invest 1981; 67: 589-96.
[http://dx.doi.org/10.1172/JCI110072] [PMID: 6894152]
[http://dx.doi.org/10.1172/JCI110072] [PMID: 6894152]
[11]
Bikle DD, Gee E, Halloran B, Haddad JG. Free 1,25-dihydroxyvitamin D levels in serum from normal subjects, pregnant subjects, and subjects with liver disease. J Clin Invest 1984; 74(6): 1966-71.
[http://dx.doi.org/10.1172/JCI111617] [PMID: 6549014]
[http://dx.doi.org/10.1172/JCI111617] [PMID: 6549014]
[12]
Forman JP, Giovannucci E, Holmes MD, et al. Plasma 25-hydroxyvitamin D levels and risk of incident hypertension. Hypertension 2007; 49(5): 1063-9.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.107.087288] [PMID: 17372031]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.107.087288] [PMID: 17372031]
[13]
Hyppönen E. Vitamin D for the prevention of preeclampsia? A hypothesis. Nutr Rev 2005; 63(7): 225-32.
[http://dx.doi.org/10.1111/j.1753-4887.2005.tb00378.x] [PMID: 16121476]
[http://dx.doi.org/10.1111/j.1753-4887.2005.tb00378.x] [PMID: 16121476]
[14]
Gestational Hypertension and Preeclampsia. ACOG Practice Bulletin, Number 222. Obstet Gynecol 2020; 135(6): 237-60.
[http://dx.doi.org/10.1097/AOG.0000000000003891]
[http://dx.doi.org/10.1097/AOG.0000000000003891]
[15]
Aydin S. A short history, principles, and types of ELISA, and our laboratory experience with peptide/protein analyses using ELISA. Peptides 2015; 72: 4-15.
[http://dx.doi.org/10.1016/j.peptides.2015.04.012] [PMID: 25908411]
[http://dx.doi.org/10.1016/j.peptides.2015.04.012] [PMID: 25908411]
[16]
Tyas BD, Lestari P, Aldika Akbar MI. Maternal Perinatal Outcomes Related to Advanced Maternal Age in Preeclampsia Pregnant Women. J Family Reprod Health 2019; 13(4): 191-200.
[PMID: 32518569]
[PMID: 32518569]
[17]
Sheen JJ, Huang Y, Andrikopoulou M, et al. Maternal Age and Preeclampsia Outcomes during Delivery Hospitalizations. Am J Perinatol 2020; 37(1): 044-52.
[http://dx.doi.org/10.1055/s-0039-1694794] [PMID: 31430824]
[http://dx.doi.org/10.1055/s-0039-1694794] [PMID: 31430824]
[18]
Vitoratos N, Chrystodoulacos G, Kouskouni E, Salamalekis E, Creatsas G. Alterations of maternal and fetal leptin concentrations in hypertensive disorders of pregnancy. Eur J Obstet Gynecol Reprod Biol 2001; 96(1): 59-62.
[http://dx.doi.org/10.1016/S0301-2115(00)00401-2] [PMID: 11311762]
[http://dx.doi.org/10.1016/S0301-2115(00)00401-2] [PMID: 11311762]
[19]
Gohil JT, Patel PK, Gupta P. Estimation of lipid profile in subjects of preeclampsia. J Obstet Gynaecol India 2011; 61(4): 399-403.
[http://dx.doi.org/10.1007/s13224-011-0057-0] [PMID: 22851820]
[http://dx.doi.org/10.1007/s13224-011-0057-0] [PMID: 22851820]
[20]
Tesfa E, Nibret E, Munshea A. Maternal lipid profile and risk of pre-eclampsia in African pregnant women: A systematic review and meta-analysis. PLoS One 2020; 15(12): e0243538.
[http://dx.doi.org/10.1371/journal.pone.0243538] [PMID: 33362205]
[http://dx.doi.org/10.1371/journal.pone.0243538] [PMID: 33362205]
[21]
Qiu C, Phung TTT, Vadachkoria S, Muy-Rivera M, Sanchez SE, Williams MA. Oxidized low-density lipoprotein (Oxidized LDL) and the risk of preeclampsia. Physiol Res 2006; 55(5): 491-500.
[http://dx.doi.org/10.33549/physiolres.930813] [PMID: 16343047]
[http://dx.doi.org/10.33549/physiolres.930813] [PMID: 16343047]
[22]
Timalsina S, Gyawali P, Bhattarai A. Comparison of lipid profile parameters and oxidized low-density lipoprotein between normal and preeclamptic pregnancies in a tertiary care hospital in Nepal. Int J Womens Health 2016; 8: 627-31.
[http://dx.doi.org/10.2147/IJWH.S117850] [PMID: 27822126]
[http://dx.doi.org/10.2147/IJWH.S117850] [PMID: 27822126]
[23]
Bodnar LM, Catov JM, Simhan HN, Holick MF, Powers RW, Roberts JM. Maternal vitamin D deficiency increases the risk of preeclampsia. J Clin Endocrinol Metab 2007; 92(9): 3517-22.
[http://dx.doi.org/10.1210/jc.2007-0718] [PMID: 17535985]
[http://dx.doi.org/10.1210/jc.2007-0718] [PMID: 17535985]
[24]
Barrera D, Noyola-Martínez N, Avila E, Halhali A, Larrea F, Díaz L. Calcitriol inhibits interleukin-10 expression in cultured human trophoblasts under normal and inflammatory conditions. Cytokine 2012; 57(3): 316-21.
[http://dx.doi.org/10.1016/j.cyto.2011.11.020] [PMID: 22182686]
[http://dx.doi.org/10.1016/j.cyto.2011.11.020] [PMID: 22182686]
[25]
Cardús A, Parisi E, Gallego C, Aldea M, Fernández E, Valdivielso JM. 1,25-Dihydroxyvitamin D3 stimulates vascular smooth muscle cell proliferation through a VEGF-mediated pathway. Kidney Int 2006; 69(8): 1377-84.
[http://dx.doi.org/10.1038/sj.ki.5000304] [PMID: 16557229]
[http://dx.doi.org/10.1038/sj.ki.5000304] [PMID: 16557229]
[26]
Robinson CJ, Alanis MC, Wagner CL, Hollis BW, Johnson DD. Plasma 25-hydroxyvitamin D levels in early-onset severe preeclampsia. Am J Obstet Gynecol 2010; 203(4): 366.e1-6.
[http://dx.doi.org/10.1016/j.ajog.2010.06.036] [PMID: 20692641]
[http://dx.doi.org/10.1016/j.ajog.2010.06.036] [PMID: 20692641]
[27]
Powe CE, Seely EW, Rana S, et al. First trimester vitamin D, vitamin D binding protein, and subsequent preeclampsia. Hypertension 2010; 56(4): 758-63.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.110.158238] [PMID: 20733087]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.110.158238] [PMID: 20733087]
[28]
Albejante MC, Kunz TCM, Ferreira MFC, et al. Proteinuria is Associated with Urinary Loss of Cubilin and Vitamin D-Binding Protein in Patients with Preeclampsia. Sci Rep 2020; 10(1): 3956.
[http://dx.doi.org/10.1038/s41598-020-60924-4] [PMID: 32127613]
[http://dx.doi.org/10.1038/s41598-020-60924-4] [PMID: 32127613]
[29]
Kalousova M, Dusilova-Sulkova S, Zakiyanov O, et al. Vitamin D Binding Protein Is Not Involved in Vitamin D Deficiency in Patients with Chronic Kidney Disease. BioMed Res Int 2015; 2015: 1-8.
[http://dx.doi.org/10.1155/2015/492365] [PMID: 26064917]
[http://dx.doi.org/10.1155/2015/492365] [PMID: 26064917]
[30]
Piquette CA, Robinson-Hill R, Webster RO. Human monocyte chemotaxis to complement-derived chemotaxins is enhanced by Gc-globulin. J Leukoc Biol 1994; 55(3): 349-54.
[http://dx.doi.org/10.1002/jlb.55.3.349] [PMID: 8120452]
[http://dx.doi.org/10.1002/jlb.55.3.349] [PMID: 8120452]
[31]
Mahmoud AM, Szczurek M, Hassan C, et al. Vitamin D Improves Nitric Oxide-Dependent Vasodilation in Adipose Tissue Arterioles from Bariatric Surgery Patients. Nutrients 2019; 11(10): 2521.
[http://dx.doi.org/10.3390/nu11102521] [PMID: 31635396]
[http://dx.doi.org/10.3390/nu11102521] [PMID: 31635396]
[32]
Ramiro-Cortijo D, de la Calle M, Böger R, et al. Male fetal sex is associated with low maternal plasma anti-inflammatory cytokine profile in the first trimester of healthy pregnancies. Cytokine 2020; 136: 155290.
[http://dx.doi.org/10.1016/j.cyto.2020.155290] [PMID: 32956948]
[http://dx.doi.org/10.1016/j.cyto.2020.155290] [PMID: 32956948]
[33]
Amiya E. Interaction of hyperlipidemia and reactive oxygen species: Insights from the lipid-raft platform. World J Cardiol 2016; 8(12): 689-94.
[http://dx.doi.org/10.4330/wjc.v8.i12.689] [PMID: 28070236]
[http://dx.doi.org/10.4330/wjc.v8.i12.689] [PMID: 28070236]
[34]
Stark MJ, Dierkx L, Clifton VL, Wright IMR. Alterations in the maternal peripheral microvascular response in pregnancies complicated by preeclampsia and the impact of fetal sex. J Soc Gynecol Investig 2006; 13(8): 573-8.
[http://dx.doi.org/10.1016/j.jsgi.2006.06.006] [PMID: 17055308]
[http://dx.doi.org/10.1016/j.jsgi.2006.06.006] [PMID: 17055308]
[35]
Broere-Brown ZA, Adank MC, Benschop L, et al. Fetal sex and maternal pregnancy outcomes: A systematic review and meta-analysis. Biol Sex Differ 2020; 11(1): 26.
[http://dx.doi.org/10.1186/s13293-020-00299-3] [PMID: 32393396]
[http://dx.doi.org/10.1186/s13293-020-00299-3] [PMID: 32393396]
