Malaysia is a tropical country where sunlight is available throughout the year. However, we have shown that the prevalence of VDD among pregnant women is high. The estimate of 82.0% of maternal plasma 25OHD < 50 nmol/L was consistent with the studies conducted in the local urban area (Kuala Lumpur). The studies reported 90% and 72% VDD (25OHD < 50 nmol/L) among pregnant women at first trimester [15] and delivery [24], respectively. However, the prevalence reported in the present study was higher compared to our previous study conducted among pregnant women from a private hospital in Kuala Lumpur [37]. The variation could be attributed to differences in the proportion of ethnicity and socio-economic background among study participants in present and previous studies. The prevalence of maternal deficiency reported in the present study was comparable to the prevalence reported in countries at high latitude, which included Ireland (80.0%) [38], Germany (77.0%) [39], China (75.0%) [40] and Japan (73.0%) [41]. Nonetheless, the prevalence of maternal deficiency reported in the present study is higher compared to those reported in Thailand (20–40%) [13, 14] and India (66.0%) [12] among pregnant women at delivery and third trimester.
In previous studies, the factors that had been reported to be significantly associated with maternal vitamin D status varied from study to study. These discrepancies suggest that vitamin D status is country-, ethnic- or subgroup-specific. Besides different geographically (latitude and UV availability), each country implements its dietary recommendation, vitamin D food fortification strategies and supplementation policy. Likewise, each subgroup or ethnic groups has a different eating habit, clothing, skin colour, physical activity, attitude towards sun exposure and genetic makeup. A combination and interaction of these factors may put a population at risk of VDD. From another context, to address the needs and inform the potential intervention, the novel factors associated with increased risk of VDD in a specific country, ethnic, or sub-group should be explored. In this study, we comprehensively assessed the demographics and lifestyle factors as well as GC polymorphism that associated with VDD in our study population.
Despite abundance in sunlight throughout the year, we found no association between time spent outdoors and maternal VDD. Likewise, skin type was not associated with the risk of maternal VDD. These null results are consistent with previous local studies, which examined factors associated with VDD in early pregnancy [15]. They found no association between Fitzpatrick classification, melanin indices, sun protection score and sunlight exposure with maternal VDD [15]. The null results may be driven by a high proportion of Malay ethnic group in the study, with a majority of them (82.5%) were veiled. In support of this, veiled was identified as a risk of VDD, which veiled women were about 4 times higher risk than unveiled women. This finding is expected as UVB does not transmit through clothing. This finding is in agreement with a study conducted in Saudi Arabia [42], which the investigators reported that veiled significantly associated with increased risk of VDD.
The positive association between vitamin D intake from food and supplements and maternal VDD is in agreement with some [34, 41, 43–48], but not all [39] of the previous studies. It appears that vitamin D intake from food and supplements contributed significantly to 25OHD level in population, in which sun exposure is minimum or dermal synthesis of 25OHD is limited. For instances, recent studies from two high latitude countries, Sweden [49] and Switzerland [34, 47] reported that supplements use, but not time spent outdoors was associated with decreased risk of VDD. Likewise, in a large Chinese study, Yun and colleagues [40] demonstrated that vitamin D supplements use was associated with vitamin D status during winter when the sun exposure is limited but not significantly associated during autumn. Our study produced results that corroborate with their findings, in which sun exposure did not contribute to the risk of VDD, but dietary vitamin D intake did.
Previous studies investigating the association of GC rs7041 with 25OHD had demonstrated C allele associated with decreased risk of VDD in pregnant [25–27, 50] and non-pregnant population [19–22]. In contrast to the previous studies, the C allele was found to increase the risk of VDD in pregnant women in the current study. The discrepancy could be due to the factors included in the present studies were different from previous findings. For instance, the previous studies that examined the factors associated with maternal VDD have been restricted to the only environmental [15, 23, 24] or genetic variables alone [25–28]. Additionally, it is possible that changes in the metabolism of vitamin D, notably elevation of circulation vitamin D binding protein concentration, may change the association of GC SNP with vitamin D status. The discrepancy suggests that the tremendous change in the metabolism of vitamin D during pregnancy may cause a differential in the factors associated with VDD in pregnancy compared to the non-pregnant state.
This study has the limitation as the data was collected in a public hospital in which the study finding may not be generalised to the pregnant women who attend the private Hospital. However, this study assessed a wide range of possible factors associated with maternal VDD: vitamin D intake from diet and supplements, estimates of sun exposure, skin type, clothing and SNPs. Owing to limited resources, the sample size of this study is small. This had limited the number of SNPs that could be studied in the present study. Nonetheless, we have selected two SNPs (rs4588 and rs7041) that most reported associated with 25OHD in the previous studies. The sample size of the current study had a sufficient power to detect the prevalence and the associations of the demographics, lifestyle and VDBP SNPs (or diplotypes) with maternal VDD.
The high prevalence of maternal VDD reported in this study indicates the need for urgent development and implementation of strategies to improve maternal vitamin D status. In Malaysia, where sunlight is available throughout the year, advocating increasing sunlight exposure will be a cost-effective measure. Nonetheless, as a large majority of Malaysian women are veiled, advocating sun exposure may not increase the 25OHD level in the majority of them. Veiled is a non-modifiable risk factor almost all of the Malay women are veiled for the religious requirement. Given that the food source of vitamin D is limited, it appears that the potential strategy to increase 25OHD level in pregnant women is vitamin D supplementation. To support this, our study found a significant association of vitamin status with vitamin D intake from the supplement. However, less than half (40.1%) of the study participants took a vitamin D containing supplement, and among the supplement users, prenatal multivitamin was the most prevalent supplement (66.7%) consumed. Most of these pregnant women obtained their prenatal multivitamins (containing 10 µg of vitamin D per capsule) from public health clinics during their antenatal visit while few of them bought the supplement themselves. It should be noted that in the Malaysian public health clinic, the provision of prenatal multivitamin D is not universal. However, the provision is dependent on the availability and the requirement of pregnant women. Taken together, this study suggests that the universal provision of a prenatal multivitamin may be effective in improving the vitamin D status of pregnant women. Investigating the effectiveness of supplement pregnant women in randomised controlled trials could be the next step if to develop national recommendations or policies for supplementation. Additionally, the significant association of GC SNPs (and GC diplotypes) with maternal VDD showed in the present and the previous study suggests that supplementation should be more personalised based on genotype and risk factors assessment, particularly in pregnant women.