http://informahealthcare.com/jmfISSN: 1476-7058 (print), 1476-4954 (electronic)

J Matern Fetal Neonatal Med, Early Online: 1–4! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2014.924103

ORIGINAL ARTICLE

Severe vitamin D deficiency among pregnant women and theirnewborns in Turkey

Mesut Parlak1, Salih Kalay2, Zuhal Kalay3, Ahmet Kirecci4, Ozgur Guney5, and Esad Koklu2

1Division of Endocrinology, Department of Pediatrics, Kahramanmaras Necip Fazıl City Hospital, Kahramanmaras, Turkey, 2Division of

Neonatology, Department of Pediatrics, Kahramanmaras Necip Fazıl City Hospital, Kahramanmaras, Turkey, 3Department of Pediatrics,

Kahramanmaras Necip Fazıl City Hospital, Kahramanmaras, Turkey, 4Department of Obstetrics and Gynecology, and 5Department of Biochemistry,

Kahramanmaras Necip Fazıl City Hospital, Kahramanmaras, Turkey

Abstract

Objectives: Vitamin D deficiency is an important health problem in pregnant women and theirinfants in sunny countries. Low socio-economic status (LSES), covered dressing style,pregnancies in winter season and having dark skin are the major risk factors for vitamin Ddeficiency. The present study evaluated serum 25-hydroxyvitamin D3 [25(OH)D3] concentra-tions in pregnant women and in their newborns and determined the risk factors in LSES cities inTurkey.Methods: Ninety-seven pregnant women and their newborns were included in the studybetween December 2012 and February 2013. All of the pregnant women had irregular follow-up or had received no antenatal care, were pregnant during summer, had presented to thehospital after 37 weeks of gestation (WG) and had received no vitamin D supplementation.A detailed history was obtained, which included mothers’ age, number of births and dressingsytle. Maternal and cord blood samples were taken to measure 25(OH)D3 levels.Results: All of the pregnant women were predominantly LSES, had covered dressing style andnone of them had received vit D3 supplementation during pregnancy. The mean serum25(OH)D3 level and mean cord blood level of of 97 mothers were 4.97 ± 3.27 ng/ml and4.29 ± 2.44 ng/ml, respectively. There was a strong positive correlation between maternal serumand umbilical cord 25(OH)D3 levels (r: 0.735, p50.05). Ninety-five mothers had serum 25(OH)D3below 20 ng/ml and all cord blood serum 25(OH)D3 levels were below 20 ng/ml. Level of25(OH)D3 was not correlated with mother age, WG or newborn weight. Serum 25(OH)D3concentrations in primigravida and multigravida were 3.71 ± 1.88 and 5.2 ± 3.4 ng/ml, respect-ively, with a significant difference between them (p50.05).Conclusion: Severe vitamin D deficiency is common in reproductive women and their newbornsin LSES cities of Turkey. Covered dressing style, not receiving any vitamin D supplementationand primigravida women are at greatest risk. Vitamin D supplementation campaigns whichshould cover pregnant women and the newborn to prevent maternal and perinatal vitamin Ddeficiency should be implemented especially in risk areas.

Keywords

Newborn, pregnant women, vitamin D

History

Received 24 January 2014Revised 18 April 2014Accepted 11 May 2014Published online 30 May 2014

Introduction

Vitamin D is essential for calcium and bone mineral

metabolism of the body. Major vitamin D sources of

humans are sunlight (90% of intake) and dietary intake

(%10). In the skin, ultraviolet B light activates provitamin D

to vitamin D3, which is converted to 25-hydroxyvitamin

D3 [25(OH)D3] in the liver. Serum concentration of

25(OH)D3 is a good indicator of vitamin D status. In recent

studies, vitamin D deficiency was defined by 25(OH)D3

level520 ng/ml in children and adults [1,2].

Maternal vitamin D status affects the maternal and

neonatal calcium homeostasis during pregnancy. Vitamin D

supply to the fetus occurs through placental transfer from the

mother. Concentration of newborn’s cord blood 25(OH)D3

level is correlated with that of the mother’s [2]. Vitamin D

deficiency (VDD) is an important health problem in preg-

nancy which leads to bone deformities known as rickets,

hypocalcaemia with or without convulsions, muscle weakness

and heart failure in the newborn [3]. In several studies, the

reason of VDD in pregnant women have been identified, the

main factors being living-land location, dark skin colour,

covered dressing style, pregnancies in winter season, low-

socioeconomic level, lack of supplementation of calcium and

vitamin D during pregnancy [4].

Although Turkey is a sunny country, VDD is the important

health problem in the population. There are few data about

Address for correspondence: Salih Kalay, MD, Division of Neonatology,Department of Pediatrics, Kahramanmaras Necip Fazıl City Hospital,Kahramanmaras, Turkey. E-mail: salihkalay@hotmail.com

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hypovitaminosis D in pregnancy and newborn which were

reported from cities with high socioeconomic levels in Turkey

[2,4]. The present study aims to measure serum 25(OH)D3

levels among pregnant women and their newborn, and to

investigate the factors in LSES areas.

Subjects and methods

The study was conducted between December 2012 and

Fabruary 2013 in the Department of Obstetrics and Child

Health, Kahramanmaras Necip Fazil City Hospital (lat.

37.35�N) which caters predominantly to a population

with low socioeconomic status. The study was approved

by the ethics committee of Sutcuimam University,

Kahramanmaras.

During the study period, there were 1900 normal vaginal

and caesarean section deliveries. Ninety-seven pregnant

woman and their newborns were included in the study. The

pregnant women had pregnancy during summer time,

presented to the hospital after 37 WG, had irregular follow-

up or had received no antenatal care and none of them had

received vitamin D supplementation. Exclusion criteria were

presence of chronic liver or renal diseases, thyroid or adrenal

diseases, treatment with drugs that affect bone metabolism,

obstetric problems such as gestational diabetes, preeclampsia,

eclampsia and premature delivery.

A detailed history was obtained from each woman

including age, number of birth, dressing styles (covered-

uncovered). Covered style of dressing refers to clothing that

covers the hair and arm but not hands and face, while

uncovered style was defined as head and arms uncovered.

Newborn weight nearest to 10 g (Seca, Birmingham,

United Kingtom). Newborn with normal birth weight

(42500 g) were included in the study.

Vitamin D deficiency was classified as follows: serum

25(OH)D3 level 55 ng/ml represents severe deficiency,

5–10 ng/ml moderate deficiency and 10–20 ng/ml mild defi-

ciency [2].

Measurements

Maternal venous blood samples were taken during the 3 days

before birth and newborn cord blood samples were taken at

birth. Blood samples were centrifuged for 30 minutes in the

delivery room and were then stored in �40 �C until analysis.

All samples were analyzed at Kahramanmaras Necip Fazil

City Hospital Laboratory in a single analytic run. Serum

25(OH)D3 levels were measured with ECLIA by a specific

electrochemiluminescence immunoassay (Roche Elecsys

E170 Modular Analytics, Mannheim, Germany).

Statistical analysis

Statistical analysis was performed with SPSS version 15.0

(SPSS Inc, Chicago, IL). The results were expressed as mean

and median values, and as percentage in qualitative variables.

The distribution of variables was analysed with Kolmogorov-

Simirnov test. The numeric variables were analysed using

Student’s t-test. Correlation analysis was performed to

investigate the relationship between maternal serum and

newborn cord blood 25(OH)D3 concentrations and between

parity and 25(OH)D3 concentrations of the mother and cord

blood. Correlations were studied by using Spearman’s

correlation coefficient. A p value of 50.05 was considered

statistically significant.

Results

The mean age of 97 pregnant women in the study was

27.1 ± 4.5 (range: 19–38) years. All of the women used

covered-up clothing and no one had taken any vitamin D

supplementation during the pregnancy (Table 1).

The mean maternal serum 25(OH)D3 concentrations were

4.97 ± 3.27 ng/ml and 4.29 ± 2.44 ng/ml in umbilical cord

blood. We found a strong positive correlation between

maternal serum and umbilical cord 25(OH)D3 concentrations

(r: 0.494, p50.01). Serum 25(OH)D3 concentrations were

520 ng/ml in 95 pregnant women and all newborns. Maternal

and umbilical cord 25(OH)D3 concentrations are shown in

Table 2.

The mean number of parity were 2.4 ± 1 (range: 1–6)

(Table 1). We detected significant correlation between parity

and maternal 25(OH)D3 concentrations and cord blood (r:

0.235, r: 0.269, p50.05).

Mothers’ serum 25(OH)D3 concentrations in primipar

(parity¼ 1, n¼ 17) and multipar (parity42, n: 80) were

3.71 ± 1.88 and 5.24 ± 3.4 ng/ml, respectively, with a signifi-

cant difference between the groups (p¼ 0.02), (Table 3).

The mean GW and weight of the newborns were 38.6 ± 0.6

(range: 37–40 weeks) and 3257.3 ± 379.3 g (Table 1),

respectively. There were no significant differences between

Table 1. General characteristics of the mothers and newborns in thestudy.

n

Age (years) 97 27.1 ± 4.5 (range: 19–38 y)Parity 97 2.4 ± 1 (range: 1–6)Dressing style (covered) 97 97 (100%)Multivitamin not used

during pregnancy97 97 (100%)

New born weight (gram) 97 3257.3 ± 379.3Gestational week (GW) 97 38.6 ± 0.6 (range: 37–40 weeks)

Table 2. 25(OH)D3 concentrations of mothers and their newborns.

Mother, (n: 97) Newborn, (n: 97)

Vitamin D status (ng/ml)) 4.97 ± 3.27 4.29 ± 2.44Insufficient (21–29 ng/ml) 2 –Deficient (520 ng/ml) 95 97Mild (11–20 ng/ml) 8 5Moderate (5–10 ng/ml) 24 18Severe (55 ng/ml) 62 74

Table 3. Mean maternal and umbilical cord serum 25(OH)D3 levels andvariables of parity.

Primipar(parity¼ 1,

n¼ 17)

Multipar(parity42,

n¼ 80) p

Maternal 25(OH)D3 (ng/ml) 3.71 ± 1.88 5.24 ± 3.4 50.02Cord blood 25(OH)D3 (ng/ml) 3.69 ± 1.37 4.42 ± 2.61 40.05

2 M. Parlak et al. J Matern Fetal Neonatal Med, Early Online: 1–4

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mother and newborn 25(OH)D3 levels with GW, mother age

and new born weigh.

Discussion

Vitamin D deficiency is a public health problem of world-

wide. In recent literature, it has been reported that women

with one or more risk factors for low serum 25(OH)D3 should

be monitored at the beginning of pregnancy [5]. In our study,

pregnant mothers were at high risk for vitamin D deficiency.

All of the cases had low socioeconomic status, had covered

dressing style and had not taken any vitamin D supplemen-

tation during pregnancy. Therefore, the most important

finding was the unexpectedly high rate of vitamin D

deficiency at pregnant women and their newborns.

Hypovitaminosis D3 among pregnant Turkish women and

their newborns were reported by a few studies. However, all

these studies were performed in high socioeconomic cities of

Turkey [6]. In Ankara, Andiran et al. reported that 46% of the

mothers and 80% of the newborns had 25(OH)D3 levels lower

than 25 nmol/L [4]. In 2003, Pehlivan et al. studied 78 women

with their infants and described that 94.8% of the mothers had

25(OH)D3 levels below 40 nmol/L (25 nmol/L in 79.5%) in

Kocaeli which is an industrial city. They reported the risk

factors for low maternal 25(OH)D3 levels as low educational

level, insufficient intake of vitamin D and covered dressing

habits [7]. In a study, 81.4% of the mothers had serum

25(OH)D3 levels in the vitamin D deficiency and 97.2% of

their neonatals had 25(OH)D3 levels below 25 ng/ml [8].

A recent study from Izmir (lat 38.25�) reported 25(OH)D3

levels of 9.52 ng/ml and 9.74 ng/ml for the mothers who had

not used multivitamin during pregnancy and had covered

dressing style. However, this study reported no data regarding

associations of vitamin D3 levels in mothers who had covered

dressing style and had not used vitamin D3 [2].

The patients in our study had major risk factors for vitamin

D deficiency such as low socioeconomic level, covered

dressing style and not using multivitamin during pregnancy.

Therefore, vitamin D deficiency was markedly lower than

20 ng/ml in 97.8% of the maternal and in 100% of the cord

blood samples. We found a strong positive correlation

between maternal serum and cord blood 25(OH)D3 levels.

We suggest that vitamin D stores of the newborn depend

entirely on the vitamin D stores of the mother and that

maternal deficiency directly affects the neonatal status,

consistent with previous reports [2,4].

Pregnant women should use as 2000 IU/day vitamin D in

the last trimester [9]. Ustuner et al. found high levels of

25(OH)D3 in pregnant women using multivitamins compared

to those who did not [10]. Although, at present, vitamin D

supplementation is a part of antenatal care program in Turkey,

adequate supplementation for pregnant women is usually not

administered which also applies for free vitamin D campaigns

for all babies in our country [2,11].

In Netherlands, 25(OH)D3 levels measured respectively

15.2 nmol/l and 20.1 nmol/l for Turkish and Moroccan women

which were lower than those found for Western women; this

was explained by covered dressing style, dark skin colour and

avoidance of sun exposure, consistent with the literature

[12,13]. Alagol et al. investigated vitamin D deficiency in

three different styles of dressing in summer and reported that

there were no differences between traditional clothing (hands

and face uncovered) and traditional Islamic style (covering

the whole body including hands and face) but described

significant differences for undressed style [14]. A study in

2003 reported vitamin D3 levels of 20.1 nmol/L for the

uncovered style group and 16.8 nmol/L for covered style

group, with significant differences between the groups [7].

Erol et al. found moderate/severe vitamin D3 deficiency

(25(OH)D3 510 ng/ml) in 70% of pregnant women with

covered dressing style [15]. Our study was conducted in an

area which traditional and religious life-style was dominant.

In addition, all subjects had covered dressing style. Vitamin

D3 levels were markedly lower than several prior studies

which were reported in literature before. These may be

explained by the main risk factor of low 25(OH)D3 levels

for mothers and newborns which are accordance with

previous studies.

A study from Greece reported that pregnant women who

delivered in spring and winter had lower 25(OH)D3 than

those who delivered in summer and that abundant sunlight

exposure was not sufficient to prevent vitamin D deficiency.

Therefore, pregnant women should be prescribed vitamin D

supplementation, both dietary and with medication [16]. Our

study examined during summer and autumn and there were no

risk factors associated with seasons for vitamin D deficiency.

Hasanoglu et al. found low serum 25(OH)D3 levels in 20% of

mothers who had their pregnancies in winter months [17]. In a

recent study, mothers who gave birth during the summer

season and their neonates had significantly higher serum

25(OH)D3 levels than mothers who gave birth during the

winter season: 18.1 ng/ml, 10.1 ng/ml, 13.9 ng/ml and 7.9 ng/

ml respectively [8]. Severe studies described vitamin D3

deficiency incidences of 45.6–50.4% (winter-spring), 46%

(autumn) and 80% (spring-summer) in different regions of

Turkey [2,4,7,10].

Our city, Kahramanmaras is ranked as the 60th city in

terms of socioeconomic level in Turkey [6]. Low socio-

economic status (LSES) is another important risk factor of

vitamin D deficiency for mothers and newborns. Women of

LSES are mostly housewives and spend most of their time

indoors and their exposure to direct sunlight is lower. Andıran

et al. identified 25(OH)D3 levels of 14.8 nmol/L for LSES

and 21.4 nmol/L for upper SES, with a significant difference

between the groups [4]. In the present study, no evaluations

based on national poverty level criteria or education level

were performed.

Primiparity can be added as another risk factor for

vitamin D deficiency in our study, although the literature

reports less frequent vitamin D deficiency in nulliparous

women and high risk for multiparity or no effect of

increasing parity on vitamin D metabolites [2,4,7,18,19].

In the present study, 25(OH)D3 levels were significantly

lower in the first pregnancy than in second or more

pregnancies and the newborns born to these mothers. Low

25(OH)D3 levels may be explained by the main risk factor

of LSES and avoidance of direct sun exposure. Our results

indicate that vitamin D supplementation should be used

during and after pregnancy by all mothers. In practice,

prenatal vitamin D supplementation should be increased to

DOI: 10.3109/14767058.2014.924103 Vitamin D deficiency among pregnant women & newborns 3

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more than 2000 IU/day for women having their first

pregnancies [9].

In this study, there was no significant association between

maternal serum 25(OH)D3 concentrations and maternal age,

gestation age or newborn weight, consistent with some

previous [2,20]. A study, however, found increasing maternal

vitamin D deficiency associated with younger maternal age

and lower infant weight [21].

In conclusion, as seen in our results, despite a sunny

environment, severe vitamin D deficiency is common in

reproductive women and their newborns in LSES cities of

Turkey. Primigravida, covered dressing style, not receiving

any vitamin D supplementation and LSES are identified as

risk factors. Routine maternal serum 25(OH)D3 measure-

ments should be recommended for pregnant women. In

addition, vitamin D supplementation should be considered for

pregnant women and newborns with risk factors.

Declaration of interest

All author’s have no conflict of interest.

References

1. Bowyer L, Catling-Paull C, Diamond T, et al. Vitamin D, PTH andcalcium levels in pregnant women and their neonates. ClinEndocrinol (Oxf) 2009;70:372–7.

2. Halicioglu O, Aksit S, Koc F, et al. Vitamin D deficiency inpregnant women and their neonates in spring time in westernTurkey. Paediatr Perinat Epidemiol 2012;26:53–60.

3. Sachan A, Gupta R, Das V, et al. High prevalence of vitamin Ddeficiency among pregnant women and their newborns in northernIndia. Am J Clin Nutr 2005;81:1060–4.

4. Andiran N, Yordam N, Ozon A. Risk factors for vitamin Ddeficiency in breast-fed newborns and their mothers. Nutrition2002;18:47–50.

5. Aly YF, El Koumi MA, Abd El Rahman RN. Impact of maternalvitamin D status during pregnancy on the prevalence of neonatalvitamin D deficiency. Pediatr Rep 2013;5:24–7.

6. http://www3.kalkinma.gov.tr/PortalDesign/PortalControls/WebIcerikGosterim.aspx?Enc=83D5A6FF03C7B4FC43121-E8457331356.

7. Pehlivan I, Hatun S, Aydogan M, et al. Maternal vitamin Ddeficiency and vitamin D supplementation in healthy infants. Turk JPediatr 2003;45:315–20.

8. Ergur AT, Berberoglu M, Atasay B, et al. Vitamin D deficiency inTurkish mothers and their neonates and in women of reproductiveage. J Clin Res Pediatr Endocrinol 2009;1:266–9.

9. American Academy of Pediatrics. Clinical report: prevention ofrikets and vitamin d deficiency: new guidelines for vitamin D.Pediatrics 2003;111:908–11.

10. Ustuner I, Keskin HL, Tas EE, et al. Maternal serum 25(OH)Dlevels in the third trimester of pregnancy during the winter season.J Matern Fetal Neonatal Med 2011;24:1421–6.

11. Hatun S, Ozkan B, Orbak Z, et al. Vitamin D deficiency in earlyinfancy. J Nutr 2005;135:279–82.

12. van der Meer IM, Karamali NS, Boeke AJ, et al. High prevalence ofvitamin D deficiency in pregnant non-Western women in TheHague, Netherlands. Am J Clin Nutr 2006;84:350–3.

13. Batieha A, Khader Y, Jaddou H, et al. Vitamin D status inJordan: dress style and gender discrepancies. Ann Nutr Metab 2011;58:10–18.

14. Alagol F, Shihadeh Y, Boztepe H, et al. Sunlight exposure andvitamin D deficiency in Turkish women. J Endocrinol Invest 2000;23:173–7.

15. Erol M, Isman KF, Kucur M, Hacıbekiroglu M.Evalution of maternal vitamin D deficiency. Turk Arch Ped 2007;42:29–32.

16. Nicolaidou P, Hatzistamatiou Z, Papadopoulou A, et al. Lowvitamin D status in mother-newborn pairs in Greece. Calcif TissueInt 2006;78:337–42.

17. Hasanoglu A, Ozalp I, Ozsoylu S. 25-hydroxyvitaminD3 concen-trations in maternal and cord blood at delivery. Cocuk saglıgı veHastalıkları Dergisi 1981;24:207–14.

18. Moghraby SA, Al Shawaf T, Akiel A, et al. Parity and vitamin Dmetabolites. Ann Trop Paediatr 1987;7:210–13.

19. Andersen LB, Abrahamsen B, Dalgard C, et al. Parity and tannedwhite skin as novel predictors of vitamin D status in earlypregnancy: a population-based cohort study. Clin Endocrinol (Oxf)2013;79:333–41.

20. Maghbooli Z, Hossein-Nezhad A, Shafaei AR, et al. Vitamin Dstatus in mothers and their newborns in Iran. BMC PregnancyChildbirth 2007;7:1–6.

21. Bowyer L, Catling-Paull C, Diamond T, et al. Vitamin D, PTHand calcium levels in pregnant women and their neonates.Clin Endocrinol (Oxf) 2009;70:372–7.

4 M. Parlak et al. J Matern Fetal Neonatal Med, Early Online: 1–4

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on 0

8/26

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use

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