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Vitamin D Status in Pregnant Women of North East India and Impact of Vitamin D Deficiency in Pregnancy on Feto-Maternal Outcome

Background: Despite of sufficient and stable sunny conditions across the equatorial countries, there has been a high prevalence of Vitamin D deficiency (VDD) in pregnancy. The reasons for increased prevalence of VDD are increased time spent indoors, dark skin, and adoption of covered clothing due to religious & cultural reasons, low socio-economic status that leads to chronically poor diet. The present study was undertaken to find Vitamin D deficiency in the pregnant women of North East India and to find the adverse feto-maternal outcomes associated with VDD. Methods: This prospective study was conducted in the Department of Obstetrics & Gynaecology, Gauhati Medical College & Hospital, Guwahati, Assam, and India over a period of one year. Sample size was 150 pregnant women attending antenatal clinic. Results: Out of 150 pregnant women 66 (44%) had deficient, 41 (27.3%) had insufficient and 43 (28.7%) had sufficient vitamin D levels. VDD was seen in extremes of age groups i.e. group ≤ 20 years and 3135 years. Multiparity and low socio-economic status was associated with vitamin D deficiency and insufficiency, no association was found between VDD and religion (Hindu & Muslim). There was significant association between Vitamin D deficiency and insufficiency and occurrence of gestational hypertensive diseases and low birth weight babies. Rate of primary caesarean section was significantly high in vitamin D deficient women. No association was found between VDD and PROM/PPROM, preterm births, gestational diabetes mellitus and neonatal jaundice.


INTRODUCTION
Vitamin D is produced endogenously following exposure of the skin to ultraviolet radiation with a small proportion derived from exogeneous dietary sources. Despite of sufficient and stable sunny conditions across equatorial countries, studies have reported high prevalence of VDD in pregnant and lactating women in such areas, ranging from 26-95% during pregnancy [1,2]. Women throughout Asia, Middle East and Africa have been consistently regarded as -high risk‖ for VDD. Despite of abundant sunshine, VDD has been recognized to be highly prevalent in India.
This paradox is explained by the fact that dark skin pigmentation is at increased risk of VDD. Increased time spent indoors and away from sunlight, liberal sunscreen use, adoption of covered clothing due to religious, cultural or aesthetic reasons and environmental pollution are factors implicated in the increased prevalence of VDD. Women living in low socio-economic strata are unable to meet micronutrient demands of pregnancy due to chronically poor diet. Inadequate access to dietary sources of vitamin D such as fish, dairy products, eggs and having vegetarian diet makes attaining sufficient vitamin D via food sources difficult. Women with one or more of these lifestyle risk factors could be considered vulnerable to VDD.
Pregnancy represents a time period where health status affects two individuals instead of one. With monumental development and growth that occurs in fetus, optimizing health status is imperative. In the pregnant women, it is believed that the primary role of vitamin D is immunomodulatory-rather than a calcium-regulating factor, although it would also retain that function. VDD has been associated with increased risk of a number of adverse maternal and fetal health outcomes. These includes an increased risk of gestational hypertensive diseases, gestational diabetes mellitus (GDM), preterm labour, PPROM/PROM, increased incidence of primary caesarean section. For the offspring there is increased risk of low birth weight (LBW), intrauterine growth restriction, neonatal jaundice, and neonatal tetany [3].

RESULTS
Out of 150 pregnant women 66 (44%) had deficient, 41 (27.3%) had insufficient and 43 (28.7%) had sufficient vitamin D levels. The mean vitamin D level of the study population was 24.52 ± 11.06 ng/ml.   This study showed significantly poor vitamin D status in pregnant women belonging to lower socioeconomic class. 54.5% of pregnant women of lower socioeconomic strata had vitamin D deficiency. However, Nimitphong and Holick M. in their study on vitamin D status in South Asia found that vitamin D deficiency is prevalent equally in lower and upper class [8].
Vitamin D deficiency was more in multiparous women as compared to primiparous in this study. Alshaikh et al. in their study also found that 66.8% of vitamin D deficient and 75.5% of vitamin D insufficient women were multiparous [6].
Vitamin D is thought to play a significant role in preeclampsia as an immune modulator. It helps by mounting an appropriate maternal immune response to the placenta preventing the release of anti-angiogenic factors into the bloodstream and modulating hypertension.
In the present 36.4% of vitamin D deficient pregnant women suffered from PIH, 22.7% developed pre-eclampsia, 4.5% ended up having eclampsia. 24.4% of vitamin D insufficient pregnant women suffered from PIH, 9.8% developed preeclampsia, 2.4 % ended up having eclampsia. Bodnar et al. USA in a case control study found positive correlation between vitamin D deficiency and development of preeclampsia [9].
Worldwide studies claim that vitamin D participates in immunological processes that prevent bacterial invasion, which may indirectly influence duration of pregnancy. Cytokines released by maternal and fetal systems in response to bacterial invasion leads to production of prostaglandins which then triggers preterm contractions. However, many studies have failed to prove this association.
In this study, 22.7% of vitamin D deficient women had preterm labour and 77.3 % had it at term and 22% of vitamin D insufficient women had preterm labour and 78% had it at term. Similarly, Lixia Yang et al. in their prospective study conducted in China to find the correlation between vitamin D deficiency and preterm birth found no evidence of an increase in preterm birth in relation with vitamin D deficiency [10].
In this study, 21.2% of vitamin D deficient pregnancies had ROM and in vitamin D insufficient group 19.5% of pregnant women had ROM and 11.6 % of vitamin D sufficient pregnant women had ROM. This study could not prove significant association between poor vitamin D as causal for rupture of membranes. Similarly, in a prospective observational study conducted in Southern China by J. Zhou et al. it was found that 20.81% of vitamin D deficient, 22.73% of vitamin D insufficient and 21.04% of vitamin D sufficient pregnant women had prelabour rupture of membranes [11].
The vitamin D receptor has been identified throughout the body, including the uterine smooth muscle and skeletal muscle. Vitamin D deficiency is associated with poor muscle performance in humans leading to increase in caesarean section. Many studies conducted worldwide have successfully proven that poor vitamin D status increases the rate of primary caesarean section.
In this study, 45.5% of vitamin D deficient pregnancies landed up having caesarean section while 48.5% had vaginal delivery and 6.1% had instrumental delivery, in vitamin D insufficient group 29.3% had caesarean delivery. In this study, vitamin D deficiency had significant association with increase in the rate of primary caesarean section. In a large prospective study conducted at Boston by Anne Merewood et al. it was found that there exists an inverse association between caesarean section and serum 25(OH)D levels. In their study 28% pregnant women with vitamin D deficiency had caesarean section when compared to 14% pregnant women with sufficient vitamin D levels to have caesarean delivery [12].
There are several evidences supporting the role of vitamin D in maintaining glucose homeostasis and the fact that VDD can lead to glucose intolerance. But very few clinical studies conducted worldwide have proven this association.
In this study, 8% of the pregnant women were diagnosed with gestational diabetes mellitus. In vitamin D deficiency group 9.1 % pregnant women developed GDM, 7.3% of vitamin D insufficient pregnant women developed GDM, whereas 7% of pregnant women with sufficient vitamin D levels developed had GDM. There was no association between poor vitamin D status in pregnancy and occurrence of GDM in this study. A case control study was conducted by Baker et al in USA, wherein they found those 5 individuals with vitamin D deficiency in 60 GDM cases and 8 individuals with vitamin D deficiency in 120 controls. The p value was 0.90 making this association insignificant [13]. Helena H et al in their study found no difference in pregnancy 25(OH)D concentration between GDM and non-GDM women (82 vs 82 nmol/L, P= 0.99) [14].
In this study, 45.5% of vitamin D deficient and 39% of vitamin D insufficient pregnant women delivered babies weighing less than or equal to 2.4 kg (LBW) whereas only 21% of vitamin D sufficient pregnant women delivered LBW babies. So, there was a significant association between vitamin D deficiency in pregnancy and low birth weight babies in this study.
Similarly, Wang et al. from their study concluded that maternal vitamin D insufficiency during pregnancy is independently associated with low birth weight and have a high risk of SGA in term fetus [15]. Sharma N et al. in their study found that the maternal mean vitamin D level in low birth weight group was 12.17 ng/ml which was significantly low in comparison with the normal birth weight group where it was 17.45 ng/ml [4].
The metabolisms of bilirubin and vitamin D happen in two separate paths, but they may affect each other since one stage of their synthesis takes place in liver. So far, few studies have examined the relationship between neonatal hyperbilirubinemia and maternal serum vitamin D.
In one case control study conducted in Iran by Shahrokh Mehrpisheh et al. it was found that there was no correlationship between neonatal jaundice and maternal and neonatal vitamin D deficiency [16]. In the present study, there was no significant association between developments of neonatal jaundice in babies born to vitamin D deficient mothers.

CONCLUSION
This study showed that the prevalence of VDD in pregnancy is astonishingly high and there was significant association between hypovitaminosis D and occurrence of gestational hypertensive diseases and low birth weight babies. Rate of primary caesarean section was significantly high in vitamin D deficient women. The paucity of clinical studies on the extent of vitamin D deficiency in pregnancy and adverse impact of it on maternal and fetal health and also the high cost of vitamin D estimation makes the universal antenatal screening and even the highrisk screening of pregnant women for vitamin D an economically challenging task. Despite a dearth of interventional evidence supporting supplementation/treatment of vitamin D in randomised controlled trial settings, it is generally accepted that supplementation/treatment is not harmful and may have some significant short and long term health benefits. Treatment of vitamin D deficient women and prophylactic vitamin D supplementation is safe and is recommended for all women who are pregnant or breastfeeding. Encouragement for moderate outdoor activity for adequate exposure to sunlight is desirable.