CLINICAL & BASIC RESEARCH SQU Med J, February 2011, Vol. 11, Iss. 1, pp. 52-55, Epub. 12th Feb 11 Submitted 24th Nov 10 Revision ReQ. 3rd Jan 11, Revision recd. 10th Jan 2011 Accepted 11th Jan 11 Departments of 1Obstetrics & Gynaecology and 2Medicine, Sultan Qaboos University Hospital, Muscat, Oman; 3Industrial Innovation Center, Rusayl, Oman; 4Department of Medicine, College of Medicine & Health Sciences, Sultan Qaboos University, Muscat, Oman. *Corresponding Author email: omayma0@hotmail.com ÿ⁄]Á£]75 nmol/L. Conclusion: If confirmed, these findings indicate the need for vitamin D replacement during pregnancy and lactation. Although not evidence based we recommend at least 1000 IU of cholecalciferol, (vitamin D3) daily. Keywords: Pregnancy; Oman; 25 hydroxyvitamin D3 (25OHD3); Vitamin D deficiency Vitamin D Status in Pregnant Omanis A disturbingly high proportion of patients with low vitamin D stores Moza Al Kalbani,1 *Omayma Elshafie,2 Mohammed Rawahi,2 Ali Al-Mamari,2 Abdullah Al-Zakwani,3 Nicholas Woodhouse4 CLINICAL & BASIC RESEARCH ADVanceS in KnoWleDGe This article is the first to draw attention to the possibility of widespread vitamin D deficiency among pregnant women in Oman. Application to Patient Care Until more is known about the vitamin D status in Omanis, we recommend that all pregnant women and lactating mothers should receive vitamin D supplements with at least 1000 IU vitamin D3 daily. Deficiency of vitamin D is common worldwide1 including the Gulf states.2,3 The latter is surprising as sunlight is abundant in the Middle East. More than 90% of our vitamin D is provided by sunlight4 and it is therefore obvious that those persons affected in Arabian countries have little sunlight exposure and a diet deficient in vitamin D. The role of vitamin D in normal physiology is complex and wide ranging. It has important immune modulating effects protecting against infection,4,5,6 autoimmune disorders7 and certain cancers, in addition to its well documented effects on the prevention of osteoporosis, fractures, falls in the elderly4,5 and impaired cognitive function.8 As we continually see patients with vitamin D deficiency in our clinics, it became important to establish whether or not vitamin stores (25OHD) are normal in a healthy Omani population. For this reason, we chose patients in their first and second Moza Al Kalbani, Omayma Elshafie, Mohammed Rawahi, Ali Al-Mamari, Abdullah Al-Zakwani, and Nicholas Woodhouse Clinical and Basic Research | 53 trimester of pregnancy as pregnancy and lactation are associated with profound alterations in calcium absorption and skeletal remodelling necessitating increased utilisation of vitamin D. Our findings are reported below. Methods Blood samples were obtained from a cohort of 103 consecutive healthy Omani patients at their first antenatal visit, usually in the first, but sometimes the second trimester. They were then assayed for serum calcium (Ca), phosphate (Phos), and serum alkaline phosphatase (ALP), which were measured by spectrophotometry, (COBAS Integra 800, Roche Diagnostics, Indianapolis, USA) on the same day. Serum samples for parathyroid hormone (PTH) were measured by immunochemiluminesence (Access 2, Beckman Coulter, Inc., CA, USA), and 25(OH)D3 by the LB211 gamma counter (Berthold GmBH & Co. KG, Bad Wilbad, Germany), having been centrifuged and deep frozen at –40º C . PTH and 25(OH)D3 were then measured on the same day at the end of the study. Statistical analysis was performed to determine the relationship between the level of serum Ca, Phos, ALP and PTH versus the level of serum 25(OH)D. We used a correlation test to calculate the significance of these relationships. As this showed no significant linear correlation, a polynomial trend curve was employed. The calculations were made for all groups of patients. Fully informed consent was obtained from each patient to extract the blood needed for the above procedures in addition to that required for routine antenatal screening. The study was approved by the Armed Forces Hospital authorities. Results Serum 25OHD3 levels were deficient (<25 nmol/L) in 34 patients, between 25 and 50 nmol/L in 67 patients (at risk) and two patients had values between 50 and 75 nmol/L. There was no significant linear correlation between 25(OH) D3 and serum Ca, Phos or ALP levels or parity. However, a significant relationship between PTH and 25(OH)D3 was observed which differed between the ‘deficient’ and the ‘at risk’ groups. This was confirmed using a polynomial curve, which had a significant correlation value of 0.55 [Figure 1]. Discussion This is the first study to report vitamin D status in normal pregnant Omanis. The results are alarming: 34% of these apparently healthy women were vitamin D deficient and a further 64% ‘at risk’ at a time when there is a critical need for calcium metabolism to be normal. A pregnant woman must provide 25 to 30 gm of calcium to support the developing foetal skeleton. Much of this demand Figure 1: Relationship between PTH (normal range 1.6–9.3 pmol/L) and 25(OH)D3 levels. There was no linear correlation between PTH and 25OHD3 levels, but using a polynomial curve, the correlation coefficient was significant at 0.55. Legend: PTH = parathyroid hormone; 25(OH)D3 = vitamin D3. Vitamin D Status in Pregnant Omanis A disturbingly high proportion of patients with low vitamin D stores 54 | SQU Medical Journal, February 2011, Volume 11, Issue 1 occurs in the third trimester when the foetal skeleton undergoes mineralisation. This demand is compensated for by an increased absorption of calcium from the gut induced by rising levels of PTH and the active metabolite of vitamin D, 1,25 dihydroxy vitamin D (1,25(OH)2D).9 At this point 25(OH)D will be utilised to make more 1,25(OH)2D and those patients with low stores will be at considerable risk for the development of vitamin D deficiency and osteoporosis in old age.10 To compound this problem, many Omani women have 6 or more children and breast feed for up to 2 years. During lactation, hyperabsorption of calcium does not occur and remineralisation of the maternal skeleton only starts after weaning when PTH, and 1,25(OH)2D levels rise, calcium absorption increases and urinary calcium levels fall, a process that may persist for months.11 Obviously, adequate stores of 25(OH)D are vital during this period, otherwise skeleton remineralisation will be seriously impaired and possibly result in the development of osteoporosis in old age.4,5 Interestingly, none of the patients in the 25(OH)D3 deficiency group were symptomatic and serum PTH and ALP levels were still within the normal range. However there was a significant increase of the percentage rise in PTH in the face of a declining 25(OH)D level suggesting the early stages of a biological response to vitamin D deficiency in the “at risk” group. In the deficiency group the reverse response was seen. Our 25(OH) D3 immunoassay results have been carefully checked and are correct. It is possible therefore that an overt rise of PTH and ALP levels has been suppressed by an oral intake of calcium in excess of 1 gm daily as this will delay the development of secondary hyperparathyroidism.12,13 Other factors such as body mass index may also be relevant14 but this was not examined here. In addition to its musculo-skeletal actions, vitamin D deficiency is reportedly associated with the development of certain cancers, the metabolic syndromes and infections, as well as type 1 and type 2 diabetes,4,5 disorders which are common in Oman. Our results confirm that vitamin D3 stores are low even in Omanis of reproductive age. These findings are similar to those reported in Saudi Arabians more than 25 years ago2 and more recently in the UAE and Qatar.3,12 It therefore seems sensible to advocate vitamin D supplementation for all pregnant women in the Middle East. At the present time, there are no clear cut recommendations as to the dose, but we recommend at least 1000 IU of vitamin D3 a day which should be continued throughout lactation. Until more is known about the daily calcium intake of Omanis, it would be prudent to advocate calcium supplementation as well.15 Conclusion This study shows that vitamin D3 scores are low in pregnant Omanis. Further studies are required to confirm these findings. Until then, we recommend supplementation with vitamin D3 (cholecalciferol) for all pregnant and lactating mothers. c o n f l i c t o f i n t e r e s t The authors reported no conflict of interest. References 1. Thacher TD, Fisher PR, Strand MA, Pettifor JM. Nutritional rickets around the world: causes and future directions. Ann Tropical Paediatr 2006; 26: 1–16. 2. Woodhouse NY, Norton W. Low vitamin d levels in Saudi Arabians. King Faisal Spec Hosp Med J 1982; 2:127–31. 3. Saadi HF, Dawodu A, Afandi BO, Zayed R, Benedict S, Nagelkerke N. Efficacy of daily and monthly high dose calciferol in vitamin D deficient nulliparous and lactating women. Am J Clin Nutr 2007; 85:1565– 71. 4. Holick MF. Vitamin D: A delightful health perspective. Nutrition Rev 2008; 66:5182–94. 5. Pearce SHS, Cheetham TD. Diagnosis and management of vitamin D deficiency. BMJ 2010; 340:b5664. 6. Holick MF. Vitamin D deficiency. Review article. N Engl J Med 2007; 357:266–81. 7. Hyponen E, Laara E, Reunanen A, Jarvelin M-R, Vertanen SM. Intake of vitamin D and risk of type 1 diabetes. A birth cohort study. Lancet 2001; 358:1500–03. 8. Llewellyn DJ, Lang IA, Langa KM, Muniz-Terrera G, Phillips CL, Cherubini A, et al. Vitamin D and risk of cognitive decline in elderly persons. Arch Intern Med 2010; 170:1099–100. 9. Affinito P, Tommaselli GA, di Carlo C, Guida F, Nappi C. 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