European Journal of Clinical Nutrition (2014) 68, 864–869 © 2014 Macmillan Publishers Limited All rights reserved 0954-3007/14 www.nature.com/ejcn

MATERNAL AND PEDIATRIC NUTRITION HIGHLIGHTS REVIEW

Maternal vitamin D status during pregnancy: the Mediterranean reality SN Karras1, P Anagnostis1, C Annweiler2, DP Naughton3, A Petroczi3, E Bili4, V Harizopoulou1, BC Tarlatzis1, A Persinaki1, F Papadopoulou1 and DG Goulis1 Vitamin D status during pregnancy is linked to bone mineralization of developing fetus, which justifies targeting sufficient levels of vitamin D in pregnant women. Despite high level of sunshine in the Mediterranean regions, maternal hypovitaminosis D remain common in these countries. The aim of this narrative review was to provide potential explanations for this phenomenon in an effort to guide future public health policies and vitamin D intakes during pregnancy. We searched Medline for publications regarding hypovitaminosis D during pregnancy in the Mediterranean region. Available studies confirmed the high prevalence of hypovitaminosis D among pregnant women in the Mediterranean regions (50–65% in most studies), resulting in severe skeletal and nonskeletal health events among the offspring. Reasons for this may rely on maternal darker skin pigmentation, poor dietary vitamin D intake, veiled clothing and reduced sunshine exposure, health policies and increased prevalence of obesity. Public health organizations should be aware of this phenomenon and develop specific policies to prevent hypovitaminosis D and its adverse outcomes in maternal and neonatal health. European Journal of Clinical Nutrition (2014) 68, 864–869; doi:10.1038/ejcn.2014.80; published online 14 May 2014

INTRODUCTION Pregnancy comprises a critical time frame in which the growing fetus is under the influence of a plethora of exogenous and endogenous factors. These factors have been hypothesized to be involved in lasting changes in the body composition, the physiology and the metabolism of the offspring. One of the biological factors is maternal vitamin D status during pregnancy. Maternal hypovitaminosis D during pregnancy has been related to several neonatal and maternal adverse health outcomes.1 On physiological basis, the developing fetus primarily obtains the necessary amounts of vitamin D for bone mineralization and other functions through adequate maternal stores.2 Therefore, optimizing maternal vitamin D status during pregnancy has been proposed by health organizations and nutrition specialists as the most efficient method for the prevention of this condition.3,4 Inspite of current recommendations,3,4 several cross-sectional observational studies conducted across Europe, including the Mediterranean regions, have shown a very high prevalence of pregnant populations with vitamin D deficiency. It is all the more surprising in that nutritional sources provide only o10% of the daily requirement of vitamin D,3,4 the remainder coming from the synthesis of vitamin D in the skin under the effect of solar radiation. The phenomenon of a just as similar or even higher prevalence of maternal vitamin D deficiency during pregnancy in southern European countries compared with central or northern ones warrants further investigation. This article aimed at listing possible explanations for this phenomenon in an effort to guide future public health policies and vitamin D intakes during pregnancy, while also providing a

brief review of the current literature. We have conducted a narrative review of the current literature of reported studies in pregnant populations from the Mediterranean region databases, including those published from 1990 to 2013. We searched Pubmed from inception to November 2013 with terms such as 'Maternal vitamin D status, Vitamin D deficiency, pregnancy, Mediterranean' and with the names of all Southern European countries, including non-European countries in the wider Mediterranean region.

VITAMIN D DEFICIENCY DURING PREGNANCY: MATERNAL AND NEONATAL COMPLICATIONS The human fetus acquires 30 g Ca2+ during gestation,5 whereas the fractional Ca2+ absorption increases up to 60%6 at approximately 250 mg/day during the third trimester.6 Previous concepts regarding maternal–fetal calcium balance during pregnancy are based on the classical regulatory roles of vitamin D on Ca2+ homeostasis. In this respect, it has been hypothesized that maternal 1,25-dihydroxyvitamin D increases intestinal Ca2+ absorption; thus, in the case of severe maternal vitamin D shortage, normal fetal mineral accretion could also be affected.6 This model has been strengthened by experimental data in which maternal vitamin D status had been shown to enhance placental Ca2+ transport and the maternal administration of the synthetic vitamin D analog 1-α-hydroxy-cholecalciferol has been shown to result in increased fetal Ca2+ milieu.7 These bio-phenomena have been suggested to be facilitated by the observed doubling in free calcitriol concentrations, which occurs

1 Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2Division of Geriatric Medicine, Department of Neuroscience, Angers University Hospital, Angers, France; 3Schools of Life Sciences, Kingston University, Kingston Upon Thames, London, UK and 4First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece. Correspondence: Dr SN Karras, Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Papageorgiouâ General Hospital, Medical School, Aristotle University of Thessaloniki, Venizelou 34 b Ring Road, Thessaloniki 54601, Greece. E-mail: [email protected] Received 3 December 2013; revised 7 February 2014; accepted 11 March 2014; published online 14 May 2014

Vitamin D status in pregnancy SN Karras et al

865 through upregulation of Cyp27b1 expression and activity in the maternal kidneys in the third trimester of pregnancy.8 Accumulated body of evidence, however, diversified previous concepts to calcitriol-independent mechanisms for the upregulation of Ca2+ transport during pregnancy. It has been argued that the increased 1,25-dihydroxyvitamin D3 concentration is not the responsible mechanism for increased intestinal Ca2+ absorption as other bio-peptides, such as parathyroid hormone-related peptide, prolactin, estradiol and placental lactogen, also increase during pregnancy.9 These data are supported by observations in pregnant, vitamin D-deficient or null vitamin D receptor mice in which high rates of intestinal absorption are also evident.10,11 The 25-hydroxy-vitamin D (25(OH)D) molecule crosses the placenta, such that cord concentrations are at a level of 80% compared with maternal measures.2 Previous experimental and observational data indicate pregnancy as a high-risk state for vitamin D deficiency.1,2 Consequently, in clinical terms, a neonate with sufficient vitamin D concentrations indicates adequate maternal vitamin D stores, especially during the third trimester of pregnancy.3 Pregnancy is a unique, dynamic state in which significant changes in several parameters of maternal vitamin D equilibrium, such as Vitamin D binding protein, are evident. Hence, reference ranges of 25(OH)D during normal pregnancy and lactation are difficult to set. With respect to criteria for vitamin D status in healthy individuals, the US Endocrine Society guideline addressed the evaluation and treatment of patients with specific diseases who are at risk for vitamin D deficiency,3 whereas the 2011 US Institute of Medicine (IOM) recommendations addressed the dietary reference intake of vitamin D in the normal, healthy North American population. The US IOM report relies primarily on the systematic reviews conducted by the US Agency for Healthcare Research and Quality.4 The 2011 US IOM report followed the dietary reference intake paradigm and provided recommendations for Estimated Average Requirement (the median intake needs of the population), Recommended Dietary Allowance (2 s.d. above the median needs that would meet the requirements of ⩾ 97.5% of the population) and tolerable upper intake level (the highest daily intake that is likely to pose no risk) according to age and sex. The 25(OH)D levels recommended as 'cutoffs' to define vitamin D deficiency differ between the US IOM report and the US Endocrine Society guideline. The US Endocrine Society guideline defines vitamin D deficiency as 25(OH)D o20 ng/ml (50 nmol/l), vitamin D insufficiency as 25(OH)D between 21 and 29 ng/ml and the safety margin to minimize the risk of hypercalcemia as 25(OH)D equal to 100 ng/ml (250 nmol/l). On the other hand, the US IOM report concluded that a 25(OH)D concentration equal to 20 ng/ml (50 nmol/l) covers the requirements of ⩾ 97.5% of the population, and 25(OH)D >50 ng/ml (125 nmol/l) should raise concerns about potential adverse effects. The difference in these recommendations reflects different views on current evidence worldwide. Although the IOM report targets adults and not pregnancy, by applying IOM criteria in clinical practice, the reported prevalence of vitamin D deficiency in pregnancy ranges from 20% to 84% worldwide, depending on geographical and ethnic parameters. Measured prevalence is estimated to be 18% in United Kingdom,12 25% in United Arab Emirates,13 42% in Northern India,14 50% in non-European ethnic minority women in South Wales15 and 61% in New Zealand.16 Although a relative dearth of elegant observational data17,18 suggested that maternal vitamin D insufficiency during pregnancy adversely influences all aspects of offspring skeletal health, present prospective data regarding maternal vitamin D supplementation for optimization of offspring's bone mass are conflicting.19,20 Maternal vitamin D deficiency during pregnancy has been also associated with a plethora of adverse neonatal and maternal health outcomes, some manifesting stronger associations than others.21–23 Maternal vitamin D deficiency through pregnancy has been associated with glucose intolerance and © 2014 Macmillan Publishers Limited

gestational diabetes mellitus. A positive correlation among vitamin D concentrations, insulin sensitivity and fasting and postprandial glucose concentrations at mid-gestation has been reported.24,25 A recent meta-analysis 26 on the existing observational data regarding the role of maternal vitamin D status in the development of gestational diabetes mellitus indicated a significant inverse relation of maternal serum 25(OH)D and the incidence of gestational diabetes mellitus. In addition, nested, case–control studies revealed a twofold to fivefold higher risk of severe preeclampsia in vitamin D-deficient women, indicating its role as an independent risk factor for the development of preeclampsia.27–29 Vitamin D deficiency has been also related to an increased risk of preeclampsia in a systematic review and metaanalysis of eight observational studies with high heterogeneity.30 Although a strong theoretical basis among vitamin D status during pregnancy and its impact on glycemic and hypertensive disorders is evident through immunological and placental mechanisms, available studies differ considerably in their design as well as definition of vitamin D status, parameters that affect data interpretation. Observational data also suggest a link between maternal vitamin D deficiency during pregnancy with an increased risk of several adverse pregnancy outcomes, including infections, fetal growth restriction and caesarean section. Two recent systematic reviews of current literature indicated an association of low maternal vitamin D status ((25(OH)D o50 nmol/l or o20 ng/ml)) with an increased risk for small-for-gestational-age births and bacterial vaginosis.31,32 The issue of low maternal vitamin D concentrations during pregnancy has been also hypothesized to affect the offspring’s immune profile by increasing the risk of childhood asthma, wheezing, rhinitis and eczema through a U-shaped association.33 These findings are in accordance with the known role of vitamin D on immune tolerance. Although further trials are undoubtedly needed, the exhaustive evaluation of observational data and the efforts of health organizations during the last years have highlighted the importance of this public issue. The absence of criteria for hypovitaminosis D during pregnancy is a deterring factor for setting the high prevalence of maternal hypovitaminosis D in the context of relevance to human health rather than simple biochemical testing. Further investigation, based on accurate measurements of vitamin D metabolites, is warranted to establish optimal concentrations during pregnancy in an attempt to prevent maternal morbidity and developmental deficiencies. MATERNAL VITAMIN D STATUS IN THE MEDITERRANEAN PREGNANT POPULATIONS Maternal hypovitaminosis D during pregnancy comprises a heterogeneous clinical issue as low vitamin D levels at various trimesters have been related to different birth outcomes. Currently, maternal hypovitaminosis D is defined with the same criteria for each trimester. The major advantage of studies conducted at birth is the opportunity to assess maternal–fetal dynamics of vitamin D equilibrium. Maternal vitamin D concentrations at birth could be considered as reliable markers for estimating both maternal vitamin D status during the last trimester of pregnancy and neonate concentrations at birth. Several adverse pregnancy and offspring outcomes, including preeclampsia and gestational diabetes mellitus,23–25 and offspring bone development1,33 have been associated with maternal hypovitaminosis D in all trimesters of pregnancy, whereas data regarding similar associations with other outcomes, including the mode of delivery (higher risk of Caesarean delivery with vitamin D deficiency) and preterm births, are primarily based on third trimester studies.31,32 On the other hand, bacterial vaginosis is associated with maternal vitamin D deficiency in the first trimester of pregnancy.32 European Journal of Clinical Nutrition (2014) 864 – 869

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European Journal of Clinical Nutrition (2014) 864 – 869

Abbreviation: 25(OH)D, 25-hydroxy-vitamin D.

62 mother–neonate pairs At birth

60 mother–neonate pairs At birth Greece Karras et al.2

Spain

Italy Cadario et al.

36

258 mother–neonate Third trimester pairs 1820 mother–infant pairs First trimester Morales et al.34

Perez-Lopes et al.

Narchi et al.40

Halicioglou et al.39 Turkey

United Arab Emirates Spain 35

Italy Gaggero et al.

55.5% of neonates were vitamin D deficient ( o20 ng/ml or 49.9 nmol/l) in cord blood 40 women had o 20 ng/ml or 49.9 nmol/l, with a further 11 between 21–29 ng/ml (50–75 nmol/l)

Older criteria for vitamin D deficiency used. Mothers with darker skin had lower serum 25(OH)D All women equally vitamin D deficient regardless of their skin pigmentation Cord blood concentrations of vitamin D metabolites not evaluated Non-Caucasian ethnicity, season at sampling and nulliparity were factors related to deficient 25(OH)D concentrations Maternal serum 25(OH)D levels related strongly to uncovered dressing style Higher maternal 25(OH)D levels were associated with improved infant mental development Maternal skin pigmentation was a risk factor for neonatal hypovitaminosis Neonatal vitamin D dynamics are primarily dependent on maternal ones 24 (19.5%) mothers had hypovitaminosis D, and 29% of their infants were also deficient Half of the mother–neonate pairs deficient at term 23% were at the sufficient vitamin D range, immediately after birth Median 25(OH)D: 27.4 ng/ml (68.39 nmol/l). Only 35.9% of mothers had 25(OH)D (⩾30 ng/ml) Maternal and neonatal mean 25(OH)D were 11.5 ± 5.4 and 11.5 ± 6.8 ng/ml, respectively Median plasma value of 25(OH)D3:29.6 ng/ml 123 mother–neonate At birth pairs 24 mother–neonate pairs From birth until 12 months postpartum 75 pregnant women From early pregnancy to 6 months postpartum 502 pregnant women First trimester 37

Nikolaidou et al.38 Greece

Main finding Trimester No. of subjects Country of origin Reference

Summary of available cohort studies regarding maternal and neonatal hytpovitaminosis D in the Mediterranean region

Table 1.

These data suggest that hypovitaminosis D may occur at any time of pregnancy. It is thus crucial to determine whether pregnant women are more likely to exhibit hypovitaminosis D during the first, the second or the third trimester of pregnancy. Further studies are needed to confirm this observation and to determine whether exposure to hypovitaminosis D has different effects on the newborn depending on the trimester of pregnancy. On this basis, data from pregnant Mediterranean cohorts assessed maternal vitamin D concentrations at various trimesters focusing mainly on maternal–neonate vitamin D status (Table 1). Previous studies have shown a high prevalence of vitamin D deficiency among neonates and their mothers in Southern Europe. For instance, Morales et al.34 reported data from 1820 mother–infant pairs (mean 13.5 ± 2.1 weeks of gestation). Although the primary end point of the study was directed toward the neuropsychological development of the infants, data analysis demonstrated a median plasma value of 25(OH) D3 in pregnancy of 29.6 ng/ml (73.88 nmol/l). These findings were also evident in 502 pregnant women living in the Spanish Mediterranean seacoast35 at latitude 36°N, therefore at a high sun exposure area, in the first trimester of pregnancy (gestational week 11–14). Pregnant women were classified as Spanish Caucasians and Arab immigrants. The median serum 25(OH)D concentration for the entire sample was 27.4 ng/ml (68.39 nmol/l) (interquartile range (IQR) 20.9–32.8). Only 35.9% of the participants had adequate serum 25(OH)D concentrations (⩾30 ng/ml or 75 nmol/l), whereas these concentrations were found to be insufficient (20–29.9 ng/ml or 50–75 nmol/l) in 41.4% and deficient (o 20 ng/ml or o 50 nmol/l) in 22.7% of participants. Vitamin D status was lower in Arab women compared with Caucasian women. Regression analysis determined that non-Caucasian ethnicity, season at sampling (fall/winter) and nulliparity were factors related to deficient 25(OH)D concentrations. Data from these studies indicate that Spanish pregnant women manifest a high prevalence of first trimester-impaired 25(OH)D concentrations, even though they reside in a sunny Mediterranean region. In a recent cohort study including 62 mother–neonate pairs from Northern Italy (32 infants were born to Italian mothers with very fair/fair skin and 30 to non-Caucasian mothers with dark skin),36 a 55.5% prevalence of vitamin D deficiency (o 20 ng/ml or 49.9 nmol/l) in cord blood was reported. Of note, all mothers had used daily a standard prenatal multivitamin containing 400 IU of vitamin D3. Vitamin D deficiency was more profound in neonates born of immigrant mothers. Although phototype evaluation was not standardized, this study indicates that skin pigmentation, according to the mother's country of birth, is a key risk factor for the development of neonatal vitamin D deficiency among women residing in the same geographical region. These data were not confirmed by another small study from Northern Italy in which white and black pregnant women with no supplementation were equally deficient in vitamin D.37 Although vitamin D nutritional intake and BMI values and sunshine exposure were not provided in this study, the absence of correlation between maternal skin pigmentation and hypovitaminosis D could be attributed to the small sample size (n = 24). Data from Greece are also limited. Nikolaidou et al.38 first reported data from a cohort of 123 healthy mother–newborn pairs recruited from a public hospital in the sunny Athenian region (latitude 38° N) between June and May. Skin maternal phototype and dietary calcium and vitamin D intakes were evaluated using food frequency questionnaires from mothers, none of whom was receiving vitamin D supplements. Using serum 25(OH)D concentrations o10 ng/ml (o 24.96 nmol/l) as the threshold for vitamin D deficiency,5,8,9 24 (19.5%) mothers had hypovitaminosis D. Seven of the 24 (29%) neonates of mothers with vitamin D deficiency were also deficient, whereas only 3 of the 99 (3%) neonates of mothers with normal vitamin D status were deficient (P o 0.0001, odds ratio (OR) 9.6, 95% confidence interval (CI)

Comment

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867 2.68–34.5). Mothers with darker phototypes had lower concentrations of serum 25(OH)D (16.5 ng/ml (41.184 nmol/l) and 13.6 ng/ml (33.945 nmol/l) in phototypes II and III, respectively) than those with fair phototype (18.6 ng/ml or 46.42 nmol/l). Recent data from our group2 confirmed the high prevalence of maternal vitamin D deficiency in Greek pregnant women in Northern Greece. All vitamin D forms were quantified in 60 mother–neonate paired samples (gestational week 37–42) by a novel liquid chromatography-mass spectrometry (LC-MS/MS) assay. Thirty-six women were on calcium supplementation (range 250–1000 mg/ day, with 32 on 500 mg/day) and none on vitamin D supplementation. The frequency distribution revealed 40 women o20 ng/ml or 49.9 nmol/l, with a further 11 between 21–29 ng/ml (50–75 nmol/l), leaving a minority in the sufficient range. Notably, although the pattern of neonatal 25(OH)D concentrations roughly followed the same with that of the mothers in the deficient and insufficient mother groups, it varied widely resembling uniform distribution in the group of mothers with sufficient vitamin D status. Although the study was not designed for this purpose, a high prevalence of maternal vitamin D insufficiency and deficiency was detected in a sunny European area, such as Northern Greece. A similar pattern of distribution between maternal and neonatal 25(OH)D concentrations was observed, with 25(OH)D3 being the most abundant circulating vitamin D form in both mothers and neonates. Data from Greece indicate a high prevalence of maternal vitamin D deficiency from both southern and northern country regions. The study from our group using LC-MS in both maternal and neonatal samples confirmed that neonatal vitamin D dynamics are primarily dependent on maternal ones. Of note, mother’s age was independent of vitamin D intake (r = − 0.93, P = 0.483), negatively correlated with UVB exposure (r = − 0.304, P = 0.019) and weakly negatively correlated with Ca intake (r = − 0.244, P = 0.062). Recent data from a cohort study from the Mediterranean seacoast of Turkey has also evaluated maternal vitamin D status and defined factors associated with maternal serum 25(OH)D concentrations among 258 healthy pregnant women (gestational week ⩾ 37) and their neonates.39 Mean 25(OH)D concentrations of the mothers and their infants were 11.5 ± 5.4 ng/ml (28.70 ± 12.8 nmol/l) and 11.5 ± 6.8 ng/ml (28.70 ± 16.97 nmol/l), respectively. Maternal serum 25(OH)D concentrations related strongly to factors such as uncovered dressing style. About half of these women had a veiled dressing style. The 25(OH)D concentrations of these veiled dressing mothers and their infants were 9.7 ± 5.1 (24.2 ± 12.7 nmol/l) and 9.7 ± 5.6 ng/ml (24.2 ± 13.6 nmol/l), respectively, which were significantly lower compared with those mothers who did not use the veiled dressing style. Hypovitaminosis D is also highly prevalent in pregnant populations in the Middle East.40 Longitudinal data from a prospective study in a cohort of 75 pregnant women from the United Arab Emirates indicated that only a minority (23%) were at the sufficient vitamin D range immediately after birth. Cord blood concentrations of vitamin D metabolites were not evaluated in this study. Data from Turkey and United Arab Emirates incorporate particular sartorial habits that have been found to significantly affect maternal vitamin D concentrations in both studies. Overall, the results of the above observational reports across Mediterranean countries showed a high prevalence of pregnant populations with vitamin D deficiency. However, it should be noted that vitamin D status depends on non-modifiable environmental factors (for example, latitude, local climate and season), modifiable life habits (for example, clothing, eating habits and sun exposure) and non-modifiable parameters (for example, ethnicity, skin pigmentation, skin thickness and age). Even if our research agenda focused only on Mediterranean regions (with generally high and similar rates of sunshine) and even if it is recognized that 80% of vitamin D comes from the © 2014 Macmillan Publishers Limited

cutaneous synthesis under effect of the sun, we recognize that these other factors should be taken into account. For this reason, the heterogeneity between the studies selected in this review limits the interpretation of results. Further studies should be conducted with an effort at homogenization or at least by stratifying or adjusting for these potential confounders. POSSIBLE REASONS FOR THE MEDITERRANEAN PARADOX Previous recommendations have identified higher latitude, winter season, dark pigmentation, limited sun exposure and full-body clothing as global risk factors for vitamin D deficiency.3–5,41 Data on vitamin D status from different population groups cannot be universally applied to the entire age and geographical spectrum. Each population group, such as adults, children and pregnant women, exhibits distinct behavioral parameters, which affect the vitamin D status. Available data on maternal vitamin D deficiency across Europe indicate an aggravation of this public health issue in Southern European regions with a hypothetical excess of sunshine hours.5–9 In the case of the Mediterranean region, social communities share several common climate and lifestyle characteristics, which could partially explain this paradox. Latitude Ultraviolet (UV) exposure decreases markedly with increasing latitude.41 It seems logical that Northern European countries with higher latitudes would report higher prevalence of vitamin D deficiency compared with the European South. However, a previous study in 824 elderly people in 11 European countries showed a positive relation between wintertime vitamin D status and latitude with lowest concentrations of 25(OH)D in the southern part of Europe.42 Although almost all European Mediterranean countries are located at a high latitude (37–38° N) and photosynthesis of pre-vitamin D3 is low in winter, countries with higher latitudes in Central and Western Europe (latitudes 46–81° N) report just as similar or even lower prevalence of maternal vitamin D deficiency.43 It becomes obvious that additional parameters, which are evident in the Mediterranean region, are implicated in the pathogenesis of this complex clinical entity. Skin pigmentation A major determinant of UV absorption in humans is the degree of skin pigmentation.41 The latter is determined by genetic factors. Pale skin absorbs a larger amount of UVB compared with the darker skin. Almost all previous Mediterranean data35,36,38–40 indicate increased skin pigmentation as a significant risk factor for the development of vitamin D deficiency in critical time frames, such as pregnancy. Most residents in southern Europe, including pregnant women, have a more pigmented skin, probably with less efficient vitamin D production. Moreover, the use of sunscreen during seasons with increased sunshine could comprise an additional risk factor for the decrease in UV absorbance, especially in dark-pigmented populations. Food fortification Previous data demonstrated positive effects of mandatory fortification of vitamin D status during winter in both young adults and children.44,45 Although dietary sources are a minor source of vitamin D stores, the high consumption of fatty fish (as high as 400 IU of vitamin D) in Northern European countries46 could also result in higher dietary vitamin D intakes compared with Southern Europe. European Journal of Clinical Nutrition (2014) 864 – 869

Vitamin D status in pregnancy SN Karras et al

868 Type of clothing and sunshine protection Sartorial habits are a main parameter affecting vitamin D status in women from Mediterranean populations, in whom, for religious reasons, outdoor clothing hinders cutaneous vitamin D production.39,40 Previous data from regions where veiling in women is common, such as Turkey,39 demonstrated that maternal and neonatal serum 25(OH)D concentrations related strongly to factors, such as uncovered dressing style.

Mediterranean region in order to evaluate the magnitude of this issue in relation to local parameters (nutritional, social and cultural); and second, by heightening the efforts for identifying this phenomenon to the public and health organizations by enacting the procedures for a European consensus on the field, following the paradigm of IOM and Endocrine Society’s recommendations.

General behavior General sunlight exposure behavior is not considerably documented in Mediterranean pregnant populations. Data from Northern Greece2 indicate that, in their vast majority, pregnant women mostly remain within the residence and are not exposed to sunlight, especially in hours with maximal heat and UVB levels. Main reasons for this phenomenon are the avoidance of high temperatures in sunny Mediterranean climates, especially during summer and also the concern of the effect of direct sun exposure on skin cancer development.

The authors declare no conflict of interest.

Health policy In some countries, hypovitaminosis D is considered as a vital health issue for both the mother and the child, leading to the development of prevention strategies by health organizations and specialists,3,4 such as screening in high-risk future mothers and fortification of dairy products with vitamin D. Several countries, regions and institutional bodies in Northern Europe have published recommendations for the dietary intake of vitamin D,47,48 including special age groups including pregnant and lactating women. In contrast, it is largely unrecognized and underrated in several South European countries. Increased prevalence of obesity worldwide Vitamin D status is inversely associated with obesity parameters. In particular, it has been observed that 25(OH)D levels are lower in obese compared with normal-weight subjects (17 ± 6.0 vs 23.8 ± 8.7 ng/ml) and that 25(OH)D levels are negatively correlated with body weight, body mass index, waist circumference and percentage of fat mass.49 LC-MS has shown a positive relationship between vitamin D in adipose tissue and serum 25(OH)D, consistent with adipose tissue being a storage site for 25(OH)D but not specifically implying sequestration.50 These laboratory findings are consistent with clinical studies in which equal UV irradiation and also equal oral doses of vitamin D resulted in a 57% lower increase in serum 25D concentrations in obese individuals compared with non-obese.51 Taking the widespread increase in obesity prevalence into account, we can speculate that obesity may contribute in part to the vitamin D paradox in the Mediterranean region. CONCLUSIONS Current data in the field of maternal vitamin D status in the Mediterranean basin are inconsistent. Whereas the prevailing view by the European Mediterranean population has been for decades that casual exposure to sunlight provides enough vitamin D, recent elegant observational data from this region showed a very high prevalence of vitamin D deficiency among pregnant women. Pooling of current data could be considered as the primary basis for a systematic estimation of maternal vitamin D hypovitaminosis across the Mediterranean region. Moreover, better insights on the transfer of maternal vitamin D to the fetus and the time of transfer during the antenatal period are warranted for help in policy making. European medical and scientific communities can make a difference in two important ways: first, by conducting large multicentric studies among pregnant women across the European Journal of Clinical Nutrition (2014) 864 – 869

CONFLICT OF INTEREST

DISCLOSURE This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

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