Introduction

Vitamin D is an essential fat soluble vitamin and has multiple functions. Vitamin D deficiency has been suggested to impact skeletal health as well as increase the risk of a number of non-skeletal conditions such as autoimmune diseases, cancers, type 2 diabetes mellitus, cardiovascular disease, infectious diseases, skin disorders, and schizophrenia [1]. Adequate 25(OH)D levels are particularly important for women who become pregnant, because mothers have to sustain their own vitamin D stores as well as those of their fetuses [2,3]. There is growing concern about the functional impacts of maternal vitamin D on their offspring. Low maternal levels of 25(OH)D has been suggested to be associated with some adverse outcomes for the fetus and neonate such as impaired bone development, multiple sclerosis, cancer, insulin dependent diabetes mellitus, impaired function of the immune system, asthma, and atopy [4,5]. However, evidence is inconsistent. A prospective longitudinal study showed that no associations were observed between maternal 25(OH)D concentrations and a child’s intelligence, psychological health or cardiovascular system and the concentrations of 25(OH) D in pregnancy above 75 nmol/L may result in an increased risk of atopic disorders[6]. A recent study systematically reviews randomized controlled trials and observational studies of maternal vitamin D status in pregnancy on the extraskeletal health of the offspring [7]. It is suggested that vitamin D is likely to have an effect on several offspring outcomes such as a race-dependent lowering of birthweight, type I diabetes and early childhood infections. However, data are conflicted on the impact of vitamin D on the risk of allergic conditions. There is little evidence concerning the role of maternal vitamin D in pregnancy in their child autoimmune diseases. Further investigation is needed in order to confirm the effect of vitamin D deficiency during pregnancy on various diseases in childhood.

During the past several decades, numerous studies have reported a high prevalence of vitamin D deficiency among pregnant women in countries where women wear concealing clothing such as India [8], Saudi Arabia [9] and Iran [10] and countries in northern latitudes such as the United Kingdom [6] and Norway [11]. These women are at high risk of hypovitaminosis D, due to less sunlight exposure. Few studies have examined vitamin D status in Chinese pregnant women. Beijing (Northern China) lies at a latitude of 39.9°N. Chinese women avoid direct sun exposure to prevent from tanning their skin as fair complexion is culture preference in China. In recent years Beijing has experienced serious pollution. These factors may lead to an increase in the risk of vitamin D deficiency. Indeed, in a recent small sample size study[12], we found an extremely high prevalence of vitamin D deficiency (90%) in pregnant women in Beijing in spring. This condition could be even worse in winter, since the weather is cold and windy during winter in Beijing making outdoor activity less likely. Also, little is known about maternal factors influencing vitamin D status in Chinese pregnant women.

Generally, serum 25(OH)D levels depend on sunshine exposure, latitude, clothing habits, skin pigmentation as well as diet [13]. The risk factors for hypovitamin D could vary from place to place. There is considerable interest in factors that may influence vitamin D status in Chinese pregnant women. These include sunlight exposure and multivitamin use, and variables may relate to these factors such as income and education levels. Maternal pre-pregnant weight and pre-pregnant body mass index (BMI) are also included since adipose tissue has been shown to sequester vitamin D [14].

The purpose of this study was to assess the vitamin D status in pregnant women residing in Beijing in winter. In addition, we evaluated the impact of some maternal factors on serum 25(OH)D levels. The results should provide a better understanding of the maternal factors that influence vitamin D status during pregnancy and help in raising awareness as well as suggesting strategies to prevent vitamin D deficiency in China.

Subjects and Methods

Results

The influence of maternal factors on vitamin D status

Forty eight women (38.4%) had sun exposure time ≤ 0.5 h/day. The percentage of severe vitamin D deficiency was much higher in women with shorter duration of sun exposure (≤ 0.5 h/day; 58.3%) than that of women with longer duration of sun exposure (> 0.5 h/day; 36.4%). Serum 25(OH)D concentration showed a significantly positive correlation with the time of sun exposure (r = 0.332, P < 0·001; Figure 1). The concentration of 25(OH)D was lower in pregnant women with shorter duration of sun exposure (≤ 0.5 h/day, 25.3 ± 8.9 nmol/L) than that in women with longer duration of sun exposure (> 0.5 h/day; 30.3 ± 9.5 nmol/L; P = 0.003). Thirty six women (28.8%) had a sun exposure duration ≥ 1.5 h/day. The 25(OH)D concentration in these women (31.5 ± 9.4 nmol/L) were still very low. None of these women used sunscreen during the time period of this study.

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Figure 1. The correlation of serum 25(OH)D and time of sun exposure.

Scatter plot showing the relations between serum 25(OH)D concentrations and time of sun exposure (n = 125; r = 0.287, p = 0.001).

https://doi.org/10.1371/journal.pone.0085081.g001

Of the 125 pregnant women recruited, 58 (46.4%) were multivitamin supplement users. The amount of vitamin D contained in multivitamin supplements consumed ranged from 5 to 12.5 μg. Amongst supplement users, 13/58 (22.4%) were severely vitamin D deficient vs. 43/67(64.2%) of non-users (P < 0·001). Student’s t-test analysis showed that pregnant women who reported taking a multivitamin supplement had significantly higher 25(OH)D concentrations (n = 58, 32.3 ± 9.5 nmol/L) when compared with women who did not take multivitamin supplements (n = 67, 24.9 ± 8.2 nmol/L; P < 0·001).

To determine whether education levels impact vitamin D status, women were grouped by better educated women (with associate degree or higher) and less educated women. Serum 25(OH)D concentration was higher in better educated women (n = 97, 29.7 ± 10.0 nmol/L) than in less educated women (n = 28, 24.0 ± 5.9 nmol/L; P < 0·001). The percentage of severe vitamin D deficiency was much lower in better educated women (38/97, 39.2 %) than that in less educated women (18/28, 64.3%).

In multiple regression analysis, multivitamin supplement use (coefficient β = 0.357; P < 0.001) and sun exposure (coefficient β = 0.200; P = 0.018), but not education status, were significantly associated with 25(OH)D levels.

Age, weight, pre-pregnant weight, pre-pregnant BMI, gestational age, income, duration of walking, and duration of computer use were not correlated with 25(OH)D concentrations.

Discussion

The present study showed a high prevalence of vitamin D deficiency among pregnant women in the Beijing urban area (39.9 °N), northern China in winter. Over 90% of women had vitamin D deficiency (< 50nmol/l) and none of them reached normal 25(OH)D concentrations (≥ 75 nmol/L). The study confirmed the results from our previous study which was conducted in spring [12]. These studies suggest that pregnant women in Beijing are at very high risk of vitamin D deficiency in either winter or spring.

Other studies have demonstrated that vitamin D deficiency is common in pregnant women in different countries, such as 31% in southern India [8], 19.5% in Greece [20] and 5.7 % in Iran [10]. One study observed the vitamin D status in pregnant women of several ethnic backgrounds who reside in The Hague in the Netherlands (52° N). Of all subjects, 8% of Western people and most non-Western subjects (59%-84%) had vitamin D deficiency [21]. A study from Chengdu urban area (30.7°N; Southwest China) showed that the prevalence of vitamin D deficiency was 57.1% in pregnant women in spring [22]. Direct comparisons between studies are not possible due to the use of different methods and inconsistent definitions of vitamin D deficiency. It seems, however, that all pregnant women are at a high risk of vitamin D deficiency. The predominant risk factors for hypovitamin D could vary from place to place, though, generally, serum 25(OH)D levels depend on sunshine exposure, latitude, clothing habits, skin pigmentation, and diet [13].

The major source of vitamin D for humans is exposure of the skin to sunlight [17]. Thus, keeping enough sunlight exposure is important to prevent vitamin D deficiency. In our study the results showed that the concentration of 25(OH) D is positively associated with the duration of sun exposure and this is consistent with previous reports [8]. Women with duration of sun exposure less than 0.5 h/day had higher rates of severe vitamin D deficiency. This suggests that sun exposure plays a role in maintaining vitamin D levels in Chinese pregnant women in winter. In the study, 38.4% of women had sun exposure less than 0.5 h/day. In Beijing the weather is cold and windy in winter. These conditions tend to reduce the time that women spend outdoors and lead to a decrease in UV-B exposure. In addition, for cultural reasons Chinese women avoid direct sun exposure to keep their skin fair. Therefore it is necessary to educate people about the knowledge of vitamin D, especially for pregnant women. Longer duration of sun exposure may be required for Chinese pregnant women.

How much sun exposure results in adequate vitamin D synthesis? It has been suggested that in sun-rich Brisbane, Australia, between 2 and 4 minutes sun exposure per day was needed during summer months, at noon, for a Caucasian to produce enough vitamin D[23]. The exposure duration required is highly dependent on skin pigmentation. Previous experiments suggest that Indians require about three times the UV exposure as white Caucasians to produce the same amount of vitamin D [24]. Season and latitude could also influence the duration of sunlight exposure required [25]. In Beijing (39.9°N), China, how much sunlight exposure is needed for women to form sufficient vitamin D in winter? The present study showed that even with sun exposure time over 1.5h/day, the 25(OH) D concentration was still very low. This may suggest that the role of sun exposure is limited in elevating vitamin D concentration in pregnant women residing in Beijing in winter. In addition, the cold weather in Beijing also limits the area of skin exposed. Normally, in winter, only the face and hands can be exposed in Beijing. It has been reported that minimal skin exposure of arms and face will only result in a nominal production of vitamin D-3 [26]. This may explain why prolonging sun exposure time did not effectively increase 25(OH)D level in our study.

Solar zenith angle (the angle that sunlight enters the atmosphere) affects the amount and distribution of solar radiation reaching the earth’s surface [27]. Increasing solar zenith angle results in more of the UVB radiation being absorbed by the ozone layer and little reaching the Earth's surface. In addition, increasing solar zenith angle could also enlarge the area which sunlight spread and thus decrease its intensity. The angle can be changed due to changing latitude, season, and time of day [28]. Above 37° latitude, during the fall and winter months, the zenith angle of the sun is oblique, and therefore the solar UV-B photons are efficiently absorbed by the ozone layer resulting in little cholecalciferol being made in the skin [29]. Vitamin D production in human skin occurs only when incident UV radiation exceeds a certain threshold. Matsuoka et al. demonstrated that a UV-B irradiation threshold of 18 mJ/cm² was required to induce vitamin D-3 production for healthy white subjects [30]. However, the exposure level of 18–20 mJ/cm² is not generally reached during the winter above latitude 40° and a Caucasian individual in a bathing suit outside on a sunny January day would not produce endogenous vitamin D-3 [29]. Therefore, people living in high latitudes would not achieve sufficient vitamin D from sunlight exposure in winter. It has been reported that women in high latitudes have more vitamin D insufficiency [31]. Beijing lies at a latitude of 39.9 degrees north. It is not surprising that there is a high prevalence of vitamin D deficiency in pregnant women residing in Beijing in winter.

In addition, pollution may be also a factor that affects UV-B reaching the skin and reducing endogenous vitamin D production in the skin. Beijing has experienced serious pollution in recent years. It has been suggested that air pollution is one of the main factors in determining the percentage of the ground level of UVB [32]. One study in India has found that high atmospheric pollution decreases the percentage of UVB which reaches the earth surface and children in more polluted areas are at higher risk of vitamin D deficiency [33]. Other studies have also shown that the air pollution has a significant influence on vitamin D status [34,35]. Women in Beijing can not produce enough vitamin D through sunshine exposure in winter due to multiple factors. Therefore other effective measures may need to be taken to improve vitamin D status in Chinese pregnant women.

It has been reported that vitamin D supplementation can effectively improve vitamin D status [36]. A recent randomized clinical trial in non-western immigrants in the Netherlands (none Asian) found vitamin D supplementation to be more effective than advised sunlight exposure for treating vitamin D deficiency [37]. In our study nearly half of women did take multivitamins and these multivitamins did improve the vitamin D level somewhat but did not prevent vitamin D deficiency. The supplements in our study used were most commonly pregnancy-specific multivitamins, containing relatively low doses of vitamin D (between 5 and 12·5 μg/d), obviously, which does not effectively alter the outcome of high prevalence of vitamin D deficiency. Appropriate dose of vitamin D supplementation for women may be required.

Vitamin D supplementation in pregnant women has been recommended in some countries. In Canada, the adequate intake for vitamin D in pregnancy is 5 μg/d [38], while in the UK the reference nutrient intake is set at 10 μg/day [39]. Apparently, these recommended dosages do not seem adequate for Chinese pregnant women in winter. Higher amounts of vitamin D may be required, though the precise dose remains unknown. One study [40] recruited different races of women at 27 weeks gestation. Either Single (200,000 IU vitamin D) or daily (800 IU) dose of vitamin D has been effective at raising circulating 25(OH)D concentrations. However, even with supplementation, only a small percentage of women and babies were vitamin D sufficient. Research in adults suggests that a daily dietary allowance of 1000-2000 IU/day is needed to achieve a target circulating 25(OH)D value of at least 75 nmol/L [41]. However, in pregnant women, a study evaluating plasma vitamin D status has shown that vitamin D supplementation of <2000 IU/day is not effective in achieving sufficiency [42]. Another study showed that vitamin D supplementation of 4000 IU/day for pregnant women is most effective in achieving sufficiency in all women regardless of race [43]. In 2011, the US Endocrine Society endorsed the need for at least 600 IU(15 ug)/ day of vitamin D supplementation for women during pregnancy and up to 1500–2000 IU/day to maintain 25(OH)D blood levels above 30 ng/mL [16]. There is no regular vitamin D supplementation in China at this time. A hundred percent of pregnant women had vitamin D insufficiency in our study. On the basis of these findings, it seems logical that pregnant women should routinely be supplemented with vitamin D in China. However, since there is insufficient data to evaluate the effectiveness of vitamin D supplementation during pregnancy vitamin D supplementation as routine antenatal care is yet to be determined. Further high quality randomized trials are required to evaluate the safety and effectiveness of vitamin D supplementation in pregnancy.

In the present study, no women intended to use vitamin D and only 46.4% of women reported taking pregnancy-specific multivitamin supplements. A survey revealed considerable ignorance and confusion about the function of vitamin D and sources of vitamin D in Chinese women [44]. Measures should be taken to improve their knowledge about vitamin D. Treatment should be paired with health education and advice and basic knowledge of the role of vitamin D.

In the study, the 25(OH) D level was low in all subjects, but was particularly low in less educated women. Better educated women had higher serum 25(OH)D concentrations and lower rates of severe vitamin D deficiency. In addition, the group of better educated women had more multivitamin users and longer duration of sun exposure than the group of less educated women. It has also been reported that the women using dietary supplements during pregnancy is associated with education [45]. Evidence shows that people with more education are likely to have greater knowledge of health conditions and are more likely to engage in healthy behaviors [46]. This suggests that education levels are most likely to influence women’s health awareness rather than directly affect vitamin D status.

Obesity is a risk factor for vitamin D deficiency [47]. It has been reported that pre-gravid obese women had significantly lower serum 25(OH)D concentrations and dose-dependent relations between pre-pregnancy BMI and maternal vitamin D status [48]. In the present study, 25(OH)D concentration showed no association with pre-pregnancy BMI. This could be because the majority of women in our study had normal pre-pregnancy BMI. Only 4.8% of women had pre-pregnancy BMI over 25 and no women were obese (BMI ≥30.0). Therefore, there were no enough subjects who were over weight or obese for analysis of the impact of this factor on vitamin D status. In addition, self-reporting pre-pregnancy weight may influence the accuracy of the result analysis.

The limitation of this study is that all subjects were from the Beijing urban area. Their educational status and/or behavior may be different from rural areas. Therefore, the results could not represent the condition of rural women in China. Also, the study lacked dietary information. Therefore we may not analyze the possibility that dietary factor contributed to our results.

To our knowledge, this study is the first to report the influence of maternal factors on vitamin D status in Chinese pregnant women. This design allowed us to assess the impact of these factors on vitamin D status in Chinese pregnant women. The effect of prolonging the duration of sun exposure on maintaining appropriate vitamin D levels is limited in pregnant women residing in Beijing in winter. Importantly, we did have the information on multivitamin supplement usage, which allowed us to show that while pregnancy-specific multivitamin supplements improve the status in women at low risk of severe vitamin D deficiency, it does not prevent women from vitamin D deficiency in winter. Measures may have to be taken to improve vitamin D status in pregnant women in China.

Supporting Information

Acknowledgments

The authors wish to thank Yaya Qin, Xiaoqing Tan for their assistance with sample collection and recruitment for the study.