Prevalence of calcium and vitamin D deficiency and their association with feto-maternal outcomes in a sample of Iranian pregnant women

1. Introduction

Calcium and vitamin D deficiency is a global concern compromising the health of mother and infant in pregnancy [1, 2, 3, 4]. A majority of Iranian population have some degree of hypovitaminosis D deficiency, which is even more prominent in young women despite the sunny climate [5]. This is often attributed to the limited sun exposure due to the official norm of clothing for women which obliges almost full body coverage [6], along with an insufficient dietary calcium intake [7].

The maternal calcium and vitamin D status are indicative of satisfactory neonatal calcium hemostasis, skeletal maturation and bone mineralization [8]. Metabolic alterations occur to maintain a constant serum level of ionized calcium during pregnancy. It has been shown that serum concentrations of vitamin D are especially elevated in the third trimester to fulfill the fetal demand, mainly via enhancing the intestinal absorption of calcium [9, 10]. In case the level of vitamin D is below optimal and fails to suppress parathyroid hormone (PTH), PTH will stimulate maternal bone resorption [10].

Supplementation with calcium and vitamin D has been reported beneficial in prevention of several maternal and fetal complications [11, 12, 13], such as gestational hypertension, preeclampsia, neonatal death, preterm birth [14], gestational diabetes mellitus, being small for gestational age [15], maternal morbidity and mortality [16], rickets, craniotabes [17, 18] and impaired intrauterine skeletal growth [19]. Furthermore, serious consequences including hypocalcemic seizures and dilated cardiomayopathy may pose life-threatening risks on the infants [20].

The high prevalence of calcium and vitamin D deficiency in our country augments the vulnerability of pregnant women and newborns to the negative impacts of this public health issue. Currently, there are no guidelines and standard recommendations for routine administration of calcium and vitamin D supplements in pregnancy. To improve the existing policies, obtaining a full understating of the current status and identification of high-risk individuals is necessary. Thus, we assessed the prevalence of calcium and vitamin D deficiency and its correlates in this specific population and investigated the scope of associated feto-maternal complications.

2. Material and methods

3. Results

A total of 233 pregnant women with the mean age of 28.37 ± 4.12 (19–40) years were enrolled from Mostafa Khomeini ( n = 101), Mahdieh ( n = 79), Shohadaye Tajrish ( n = 23), Bahman ( n = 20) and Arash ( n = 10) hospitals in Tehran in 2013. Most of the patients were nulliparous (56.3%) and primigravid (53.2%). About 79.4% of the patients reported adequate intake of the dairy products while most of them (79.4%) have never received calcium supplementation. Regular sun exposure was reported in 184 (78.9%) while routine physical activity was recorded in 21 (9.1%). Most of the patients (59.7%) underwent cesarean delivery and the most common complication The baseline and demographics as well as the pregnancy outcomes are summarized in Table 1.

As demonstrated, most of the subjects (58.4%) had vitamin D deficiency and 12.0% suffered from severe vitamin D deficiency. Table 2 summarizes the serum levels of vitamin D, calcium, phosphorus and parathormone D deficiency. The prevalence of vitamin D deficiency was calculated to be 72,103 in 100,000 populations. However, only 8 (3.4%) patients had calcium deficiency and 4 (1.7%) patients had phosphorus deficiency (Table 2).

Table 3 summarizes the association between the serum level of vitamin D and demographics, consumption of food and supplements, physical activity, sun exposure and maternal and neonatal outcome. We found that the serum level of PTH was correlated with serum level of vitamin D ( 0.001). The years of education were adversely associated with serum level of vitamin D ( p = 0.007). The Metabolic Equivalent of Task (MET) ( 0.001) and the exercise sequence per week ( 0.001) were associated with serum levels of vitamin D. Those with severe vitamin D deficiency had significantly lower rates of sun exposure ( 0.001), higher rate of sunscreen usage ( p = 0.011) and higher BMI ( p = 0.005). Regarding the maternal complications, vitamin D deficiency was associated with higher rate of cesarean delivery ( p = 0.024) and higher rate of diastolic hypertension ( p = 0.019). We also found that vitamin D deficiency was associated with higher rate of neonatal jaundice ( p = 0.009) and higher rate of neonatal respiratory infections ( 0.001). Using the Bayesian multiple logistic regression model, we found that serum level of PTH was a significant risk factor for severe vitamin D deficiency while calcium D supplementation, MET and sunscreen were significant protective factors (Table 4). We also determined the diagnostic accuracy of PTH for distinguishing severe vitamin D deficiency in our study population. The sensitivity and specificity of PTH was found to be 0.54 (0.32–0.76) and 0.86 (0.81–0.91) respectively. We found that the overall diagnostic accuracy calculated as AUC in the ROC curve was 0.89 (0.84–0.95) with a cut-off value of 28.63 pg/mL indicating a moderate diagnostic accuracy (Fig. 1).

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Several lines of evidence suggest that vitamin D deficiency during the pregnancy is associated with adverse pregnancy outcome. In the current study we tried to investigate the prevalence of vitamin D deficiency in singleton pregnancies in capital of Iran. We found that vitamin D deficiency was adversely associated years of education, exercising, MET, sun exposure and BMI. Vitamin D deficiency was also associated with higher rate of cesarean delivery, higher rate of diastolic hypertension, neonatal jaundice and higher rate of neonatal respiratory infections. These finds suggest that vitamin D is a common health problem during the pregnancy which is associated with significant adverse pregnancy and neonatal outcomes.

Several studies have investigated the associated between the adverse pregnancy outcomes and the serum level of vitamin D [21, 22, 23, 24]. Recently, Xu et al. [24] demonstrated that low 25 (OH) D concentrations at the first prenatal visit were associated with increased risk of GDM and might be useful in identifying women at risk of GDM for performing early prevention strategies. In another study, Wang et al. [22] demonstrated that maternal vitamin D insufficiency is common during pregnancy and is independently associated with low birth weight and high risk of small for gestational age in term infants. In a systematic review, Chu et al. [21] reported that there is an association between vitamin D status and reproductive treatment outcomes achieved in women undergoing assisted reproductive techniques (ARTs). They demonstrated that vitamin D deficiency and insufficiency could be important conditions to treat in women considering ARTs [21]. These results are in line with our findings. We reported a high rate of vitamin D deficiency in our series and a strong association was found between the low birthweight, neonatal respiratory infections and NICU admission and vitamin D deficiency. As reported in our results, only a small portion of the subjects in our series received vitamin D supplementation during their pregnancy which is extremely lower that previously reported rates and recommendations [23].

In a study from The Netherlands, the mean serum level of vitamin D was significantly lower in non-western women compared to western women independent of age, socio-economic status and parity [25]. A population-based study on pregnant women and their neonates in Australia reported an overall vitamin D deficiency among 15% of mothers and 11% of neonates. Risk factors were late winter/early spring, birthplace outside Australia, dark skin phenotype, wearing a veil and younger maternal age [26]. In contrast, a country with abundant sunshine such as India has unexpectedly high prevalence of deficiencies, as over 80 percent of rural and urban women are reported to have low calcium intake, below normal vitamin D values and above normal PTH level [27, 28] with significant differences compared to men [28]. In a cohort study in Doha on over 1,800 pregnant women, almost half had vitamin D deficiency. Age below 30 years and low income, as well as inadequate sunlight exposure, daily physical activity and vitamin D supplement intake were risk factors for hypovitamosis D. This problem elevated the risk of GDM, anemia, and preeclampsia [29]. Vitamin D insufficiency and deficiency is frequent among Caucasian women with a prevalence of approximately 90% [30].

The figures seem to be similar in Iran. In a report by Bassir et al., 80% of mothers, who were evaluated at the time of delivery had vitamin D concentrations below 25 nmol/l and PTH level above normal range. However, serum calcium was within the normal range. As a result, vitamin D was nearly undetectable in newborns of deficient mothers [31]. Evaluation of serum calcium in pregnant women in Zabol, Iran showed a constant level along first, second and third trimesters, rising from 8.3 to 8.6. It was revealed that maternal serum calcium level influences the birth weight of neonates [32]. However, Abbasian et al. reported the prevalence of calcium deficiency ( 8.5 mg/dL) to be 33.5% and 25% among Iranian mothers and neonates, respectively [33].

Given the alarming status of this preventable problem, researchers have sought to improve the deficiency via supplementation. In a randomized clinical study on pregnant women at 27 weeks’ gestation, a daily dose of 800 IU vitamin D was more efficient than a single oral dose of 200000 IU vitamin D. Yet, normal level was achieved in a small ratio of treated women [34]. Although vitamin D-containing supplements help increase the serum level, conservative dosages do not have the desired effect [30]. It is suggested that 4,000 IU/day vitamin D3 is necessary to “normalize” vitamin D metabolism and improve birth outcomes including primary cesarean section and comorbidities of pregnancy with no risk of side effects [35]. In a randomized clinical trial by Asemi et al., 500 mg calcium-200 IU cholecalciferol supplements were administerd versus placebo for nine weeks. Consumption of calcium-Vitamin D co-supplements resulted in a significant reduction of serum high-sensitivity C-reactive protein, significant elevation of plasma total antioxidant capacity serum 25-hydroxyvitamin D, and calcium levels. We saw no significant change of the co-supplementation on pregnancy outcomes as well [36].

We note some limitations to our study. The sample size was robustly selected to match the calculated one which might be a heterogeneous group. However, our study had 80% power to detect significant differences regarding the pregnancy outcomes. In addition, we selected the patients form a vast area and several centers which might lead to selection bias. We recommend the future studiesto follow the neonates to assess the long-term effects of maternal vitamin D deficiency and neuropsychiatric development. Overall, further studies with larger study population and longer follow-up periods are recommended.

In conclusion, the prevalence of vitamin D deficiency during pregnancy among Iranian women is extremely high and is associated with adverse pregnancy outcomes including cesarean delivery, neonatal jaundice and neonatal respiratory infections. Low vitamin D supplementation and sun exposure, lack of physical activity and high BMI are the etiologies. Increasing the knowledge along with vitamin D supplementation during the pregnancy is recommended in Iranian population.