Vitamin D status in pregnant women visiting a tertiary care center of North Eastern India.

BACKGROUND: Studies of vitamin D (VD) physiology suggest that effects of vitamin D deficiency (VDD) could be much broader than rickets including cardiovascular disease, cancers, diabetes, infection, and allergy and pregnancy complications. Data regarding the prevalence of hypovitaminosis in pregnancy are scanty especially in north eastern part of India. Therefore, this study has undertaken with the intention to find out prevalence and outcome of hypovitaminosis of VD in pregnancy. MATERIALS AND
METHOD: In total, 177 pregnant women with singleton pregnancy, <16 weeks of gestational age, visited to antenatal clinic of our institute were consecutively enrolled for the study. The serum VD was estimated by Beckman coulter unicel DXI immunoassay system using the principle of Chemiluminescence. Incidence of vitamin deficiency and insufficiency calculated. VDD was defined as 25(OH)D levels in blood <20 ng/mL, and insufficiency of VD was defined as 25(OH)D levels <32 ng/mL. Antenatal complications, such as intrauterine growth restriction (IUGR), oligohydramnios, pre-eclampsia, preterm labor, gestational diabetes, if any, were noted. Labor and delivery information including induction of labor, mode of delivery, and newborn birth weight were noted. RESULT: In total, 177 women recruited for the study. Mean age and parity of the subjects were 26.71 ± 9.96 and 2.10 ± 1.8, respectively. For detailed statistical analysis, women were divided into three groups depending upon their VD levels: deficiency group [25(OH)D level <20 ng/mL], insufficiency group [25(OH)D level <32 ng/mL], and sufficient group [25(OH)D level >32 ng/mL]. VDD was present in 84.18% subjects. VD insufficiency was present in 12.44% of cases. There is association of preeclampsia, cesarean section, and low birth weight babies with lower level of VD.
CONCLUSION: This study showed that the prevalence of VDD in pregnancy is astonishingly high till now there is no guideline to screen antenatal women for VDD. As the test is costly even, offering it to all at-risk women may not be cost effective compared with offering universal supplementation, particularly as treatment is regarded as being very safe.

Introduction

Vitamin D (VD) is part of complex steroid hormone system long known to be involved in the bone metabolism. Recently, the prevalence of rickets has increased sparking a new interest in vitamin D deficiency (VDD). In addition, studies of VD physiology suggest that effects of VDD could be much broader than rickets including cardiovascular disease, cancers, diabetes, infection, and allergy and pregnancy complications.

During pregnancy, serum level of 1,25(OH)D increase up to twofold starting at 10–12 weeks of gestation and reaching a maximum in the third trimester.[1]

Given an increase in the active form of VD pregnant women likely have a higher cellular exposure to VD during second and third trimesters suggesting a role for VD in obstetrics well-being. Perinatal outcome to be related to VDD preeclampsia, gestational diabetes mellitus, low birth weight, preterm delivery, and cesarean section.[2345] There is wide range of actions of VD in pregnancy, including its effects on placental function and inflammatory response.[6] Proinflammatory cytokines, such as tumor necrosis factor-a, interleukin-6, and interferon-gama have been reported to be increased in pregnancies with VDD.[7] Having important immune-modulated property VD may help to setup a proper maternal immune response to placenta.[8] It also regulates key target genes associated with proper implantation of placenta.[9] VD regulates expression of human chorionic gonadotropin in syntiotrophoblast and stimulate production of sex steroids. Many studies also suggested VD has important role in glucose and insulin metabolism.[8]

Pancreatic β-cells express 1α-hydroxylase; the active form of VD binds on VD receptor on pancreatic β-cells; the VD response element is present in the human insulin gene promoter. There is also a number of evidences about the role of VD in maintaining glucose tolerance through its influence on insulin secretion and sensitivity.

The exact mechanism of altered VD metabolism in patients with preeclampsia and hypertensive disorders is not fully understood. It may be related with inflammatory mediator and effects on blood vessels.

VD could influence the pathophysiology of preterm labor as it affects the processes of inflammation and immunomodulation. The susceptibility to infection is increased in cases of VDD because of impairment of toll-like mediated induction of antimicrobial peptide cathelicidin from macrophages.[10]

A possible reason for the potential higher risk of cesarean delivery in women with lower VD concentrations was hypothesized to be reduced pelvic muscle strength leading to prolonged labor.[10]

India being a tropical country with ample sunlight throughout the year, people still suffering from VDD and it will worsen in pregnancy.

Data regarding the prevalence of hypovitaminosis in pregnancy are scanty especially in north eastern part of India. Therefore, this study has undertaken with the intention to find out prevalence and outcome of hypovitaminosis of VD in pregnancy.

Materials and Method

This prospective study was conducted in two and half-year period in one of the teaching institute of hilly north eastern India.

In total, 177 pregnant women with singleton pregnancy, <16 weeks of gestational age, visited to antenatal clinic of our institute were consecutively enrolled for the study. Gestational age of the subject was determined using definite menstrual history and or first trimester ultrasonographic scan. Written informed consent was taken from the recruited subjects. Approval was taken from the institute ethical board. Exclusion criteria were pregnant patient with >16 weeks, known history or evidence of medical disorder such as thyroid, parathyroid, or adrenal, collagen disorder, hepatic or renal dysfunction, metabolic bone disease, type 1 diabetes mellitus, and malabsorption. Women were also excluded if they had history of medication with drugs interfering with calcium and VD metabolism like anticonvulsants, corticosteroids, thiazides, and not willing to participate in the study. Detailed history was recorded from the recruited pregnant women including complete demographic details, dietary history, past medical history, previous obstetric history, and antenatal history including details of any antenatal complications. Women were advised to give 3-cc blood samples along with routine antenatal investigation. The serum VD was estimated by Beckman coulter unicel DXI immunoassay system using the principle of chemiluminescence.

Incidence of vitamin deficiency and insufficiency calculated. VDD was defined as 25(OH)D levels in blood <20 ng/mL, and insufficiency of VD was defined as 25(OH)D levels <32 ng/mL.[11] Antenatal complications such as intrauterine growth restriction (IUGR), oligohydramnios, preeclampsia, preterm labor, gestational diabetes, if any, were noted. Labor and delivery information including mode of delivery, and newborn birth weight were noted.

Statistical analysis

Descriptive statistics was used to calculate the mean ± SD. t-test unequal variance was performed to compare the mean value between the groups. All P value <0.05 within 95% confidence interval and at 5% level of significance were considered to be statistically significant.

Result

In total, 177 women recruited for the study. Mean age and parity of the subjects were 26.71 ± 9.96 and 2.10 ± 1.8, respectively [Table 1]. For detailed statistical analysis, women were divided into three groups depending upon their VD levels: deficiency group [25(OH)D level <20 ng/mL], insufficiency group [25(OH)D level <32 ng/mL], and sufficient group [25(OH)D level >32 ng/mL]. Mean VD level was 15.53 ± 7.65 ng/dL. VDD was present in 84.18% subjects. Mean VD level in this group was 12.91 ng/dL. VD insufficiency was present in 12.44% of cases. Mean VD level was 24.175 ng/dL in this group. only six subjects had sufficient VD level. There is no association of age, education, religion, rural, versus urban area. VDD and insufficiency were present in almost all (96.62%) women. There is inverse relationship between parity and VD. Mean VD level was less in women with hypertensive disorder of pregnancy (13.52 ng/dL) as compared with women with normal blood pressure (16.02) (P < 0.01) [Table 2].

Table 1

Demographic profile

Parameters	Mean
Mean age	26.71±9.96
Mean parity	2.10±1.8
Mean vitamin D level in insufficient group	24.175±2.17
Mean vitamin D level in deficient group	12.91±4.06

Table 2

Vitamin D (VD) level in various groups

Mean VD value	Mean VD value	P
VD level in PIH group 13.52 ng/dl	VD level in normotensive group 16.02 ng/dl	P 0.01
VD level in LSCS group 13.51 ng/dl	VD level in vaginal delivery group 17.57 ng/dl	P 0.000
VD level in low birth weight group 12.17 ng/dl	VD level not in low birth weight group 17.45 ng/dl	P 0.001

About 54.25% delivered vaginally and 47.14% delivered by LSCS. Women who underwent LSCS have deficiency and insufficiency of 90% and 7%, respectively, as compared with vaginal delivery who are having deficiency and insufficiency of 80% and 11%, respectively. Mean VD level in women who underwent normal vaginal delivery was 17.57 and women who underwent LSCS was 13.51. There was statistical significance difference between two groups (P-value 0.000) by t-test unequal variance.

Mean VD level was 12.17 in mothers whose babies were low birth weight as compared with 17.45 in mothers who are having no low birth weight babies (P-value = 0.001).

Discussion

In this prospective study, prevalence of VDD and insufficiency in pregnancy was 96.62%. Sunlight exposure is often the major influence on the VD status and is influenced by skin color, latitude, season as well as life style and cultural practices. Shillong is at 25.57°N 91.88°E. In the summer, the temperature varies from 23°C (73°F). In the winter, the temperature varies from 4°C (39°F). the city features a subtropical highland climate. Its summers are cool and very rainy, while its winters are cool and dry. Shillong is subject to vagaries of the monsoon. The monsoons arrive in June and it rains almost until the end of August. People keep cover themselves almost throughout the year. Staple diet is rice. Diet is also not rich in VD.

This finding of high prevalence correlating very well with other studies done in various parts of the world. In London in antenatal population, a VD level was <25 nmol/L (10 ng/mL) was found in 47% of Indian Asian women, 64% of middle eastern women, 58% in black women, and 13% of Caucasian.[12] In this study, cutoff was less; therefore, extent of deficiency was not that high. This high prevalence of VDD <20 ng/mL also observed among pregnant women in northeastern United States.[13] VDD is also noted in gulf state.[14]

There are studies which showed wide spread prevalence of VDD in India.[1516] Various reason for this high deficiency may be poor sun exposure due to modern life style, vegetarian diet, skin pigmentation, and some cultural practice, such as pardah and burkhah.

In our study, age has no relation with VDD. Parity has direct association with VDD. Repeated and unspaced pregnancy can also exaggerated the VDD, which is already present in these women.

In present study, VD level was very low in pre-eclampsic women as compared with normotensive women (P < 0.01). This finding correlating well with another study that documented VD insufficiency was associated with increased risk of pre-eclampsia, gestational diabetes mellitus, and small for gestational age babies.[17] In two other studies, women who developed pre-eclampsia were found to have lower level of VD than women who did not with <50 nmol/L associated with a fivefold increased risk of severe pre-eclampsia.[1819]

A study from Canada demonstrated that women with low circulating maternal VD level are more likely to have hypertension on pregnancy in the univariate analysis, but not the multivariate analysis.[1320] Two meta-analyses, including a meta-analysis of 31 studies, demonstrated that VD insufficiency was associated with pre-eclampsia and SGA infants.[1721]

In our study, mother of low birth weight babies were VD insufficient or deficient. There is positive association in these two parameters.

Maternal VD levels have been shown to positively correlate with birthweight centile.[22] One study from Holland showed that women with VDD had a 2.4-fold increased risk of having an SGA baby.[23] One more study found that maternal VD levels of <37.5 nmol/L in the first half of pregnancy were associated with an adjusted odds ratio of 7.5 for SGA infants in white women, but not in black women.[24] Another study from Australia found that mean birthweight was 200 g lower (P < 0.001) in babies of VDD mothers.[25] However, other studies demonstrated no relationship between maternal VD levels in the first trimester and birthweight but revealed that low VD levels in late pregnancy were linked with reduced intrauterine long bone growth and lower gestational age at delivery.[26]

Randomized controlled trials of VD supplementation in British mothers of Asian descent suggest a greater incidence of small-for-gestational-age infants born to mothers who received placebo than to mothers who received 1,000 IU of VD per day during the final trimester of pregnancy.[2728]

Mean VD level in women who underwent normal vaginal delivery was 17.57 and women who underwent LSCS was 13.51. There was statistical significance difference between two groups (P-value 0.000) in this study. Similar to our observation, one study from Boston found that VD level <37.5 ng/L had four times the odds of a Cesarean delivery than those with higher level.[29] Contrary to this study a study from Northern California found no difference in mean VD levels between women who underwent Cesarean delivery and those who did not.[30] In one randomized control trial with VD supplementation, they observed no difference in Cesarean section rates between supplemented and control group.[31] However, one study showed that there is no correlation of VDD and various adverse pregnancy outcome, such as gestational diabetes mellitus, hypertension, pre-eclampsia, intrauterine growth restriction, preterm labor, antenatal infection, bacterial vaginosis, and anemia, and neonatal outcomes, such as low birth weight baby, and neonatal intensive care unit admission.[32]

This study showed that the prevalence of VDD in pregnancy is astonishingly high. VDD is known to be linked with an increased prevalence of pre-eclampsia, Cesarean delivery, and with small infant size. Current recommendations for daily VD intake (200 IU) are inadequate to maintain serum levels of 25(OH)D in the normal range during pregnancy and lactation. Further studies are desirable to establish the serum levels and the amount of supplementation that is necessary to optimize maternal and fetal outcomes. However, VD supplementation is easy and cost-effective with a low probability of toxicity.[33] ACOG and RCOG advocate increased supplementation in antenatal women to keep serum levels of 25(OH)D in the normal range for adults (>32 ng/mL).[3435]

Limitation of the studies lies in the fact that sample size was very small and single center study.

Conclusion

This study showed that the prevalence of VDD in pregnancy is astonishingly high till now there is no guideline to screen antenatal women for VDD. As there are no data to support routine screening for VDD in pregnancy in terms of health benefits or cost effectiveness, there is a disagreement that women at high risk for VDD should have a screening test, such as, dark skin color or coverage, obesity, risk of pre-eclampsia, or gastroenterological conditions limiting fat absorption. As the test is costly even, offering it to all at-risk women may not be cost effective compared with offering universal supplementation, particularly as treatment is regarded as being very safe.

Financial support and sponsorship

This study was funded by Intramural fund for faculty North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences Shillong, Meghalaya.

Conflicts of interest

There are no conflicts of interest.