See corresponding editorial on page 273.
See corresponding CME exam on page 468.
High prevalence of vitamin D deficiency in pregnant non-Western
women in The Hague, Netherlands1,2
Irene M van der Meer, Nasra S Karamali, A Joan P Boeke, Paul Lips, Barend JC Middelkoop, Irene Verhoeven, and
Jan D Wuister
ABSTRACT
Background: Vitamin D deficiency is common in dark-skinned
persons living in northern countries. Vitamin D deficiency during
pregnancy may have serious consequences for both mother and
child.
Objective: The objective was to ascertain the prevalence of vitamin
D deficiency in pregnant women of several ethnic backgrounds who
were living in The Hague, a large city in the Netherlands.
Design: Midwives whose practice was visited by a large number of
non-Western immigrants added the assessment of serum 25-
hydroxyvitamin D [25(OH)D] to the standard blood test given to
women who visited the practice during week 12 of pregnancy. Sub-
sequently, the Municipal Health Service collected additional data
from the midwives’ files (June 2002 through March 2004): back-
ground variables, use of tobacco or alcohol or drugs, and infectious
diseases. The women were grouped ethnically as Western, Turkish,
Moroccan, and other non-Western.
Results: The vitamin D concentrations of 358 women were found in
the midwives’ files. Of these women, 29% were Western, 22% were
Turkish, and 19% were Moroccan. Mean serum 25(OH)D concen-
trations in Turkish (15.2 앐 12.1 nmol/L), Moroccan (20.1 앐
13.5 nmol/L), and other non-Western women (26.3 앐 25.9 nmol/L)
were significantly (P 울 0.001) lower than those in Western women
(52.7 앐 21.6 nmol/L). Serum 25(OH)D was below the detection
limit in 22% of the Turkish women. The differences between ethnic
groups were not confounded by other determinants such as age,
socioeconomic status, or parity.
Conclusions: The prevalence of vitamin D deficiency in pregnant
non-Western women in the Netherlands is very high, and screening
should be recommended. Am J Clin Nutr 2006;84:350 –3.
KEY WORDS Hypovitaminosis D, vitamin D deficiency, se-
rum 25-hydroxyvitamin D, pregnancy, ethnic groups, prevalence,
women
INTRODUCTION
Vitamin D deficiency is common in dark-skinned persons
living in northern countries. Vitamin D3 is produced in the skin
after exposure to sunlight or to artificial ultraviolet light. Sunlight
is less effective in producing vitamin D3 in persons with darker
skin because the ultraviolet light is absorbed by the skin pigment
(1, 2). Low sunlight exposure, covering of the skin, and a diet low
in vitamin D and calcium may also contribute to lower vitamin D
350 Am J Clin Nutr 2006;84:350 –3. Printed in USA. © 2006 American Society for Nutrition
concentrations in non-Western immigrants to northern countries
(3–5). These risk factors affect both males and females of all
ages.
Vitamin D deficiency in pregnant women may affect the
women as well as their unborn children. The deficiency could
lead to a high bone turnover, bone loss, osteomalacia, and hypo-
Downloaded from www.ajcn.org by on January 16, 2007
vitaminosis D myopathy in the mother (6, 7). Most studies of
vitamin D deficiency during pregnancy have shown negative
effects on calcium homeostasis and skeletal mineralization of the
(unborn) child, eg, the occurrence of congenital rickets, cranio-
tabes, and lower bone mineral content (8 –10). Effects on mater-
nal weight gain, fetal growth, and birth weight are conflicting and
inconclusive (11). Some researchers hypothesize that low pre-
natal and perinatal vitamin D concentrations affect the functional
characteristics of various tissues of the body (12, 13), which leads
to a greater risk in later life of multiple sclerosis, cancer, insulin-
dependent diabetes mellitus, and schizophrenia.
To ensure adequate absorption of calcium by the fetus, the
Health Council of the Netherlands recommends a higher vitamin
D intake for pregnant than for nonpregnant women (14). How-
ever, several Dutch organizations (ie, those for midwives, gyne-
cologists, and general practitioners) state that there is insufficient
evidence of a greater need in pregnant than in nonpregnant
women (15). Many of the studies of vitamin D deficiency in
pregnant women over the past 25 y found a high prevalence in
pregnant non-Western women in countries in various parts of the
world (16 –22). Information on the prevalence in pregnant
women in the Netherlands is scarce but highly relevant, because
the group at risk is large and growing: 43% of babies born in the
4 largest Dutch cities in 2002 were of non-Western ethnicity. The
aim of our study was to ascertain the prevalence of vitamin D
1
From the Municipal Health Service of The Hague, The Hague, Nether-
lands (IMM, NSK, and BJCM); the Institute for Research in Extramural
Medicine (EMGO) (PL and AJPB) and the Department of Endocrinology
(PL), Vrije University Medical Centre Amsterdam, Amsterdam, Nether-
lands; the Department of Public Health and Primary Care, Leiden University
Medical Centre, Leiden, Netherlands (BJCM); the Femme Midwives’ Prac-
tice, The Hague, Netherlands (IV); and the De Rubenshoek Primary Health
Care Centre, The Hague, Netherlands (JDW).
2
Reprints not available. Address correspondence to IM van der Meer,
Gemeente Den Haag, Dienst OCW/EGG, Postbus 12 652, 2500 DP Den
Haag, Netherlands. E-mail: i.vandermeer@ocw.denhaag.nl.
Received December 1, 2005.
Accepted for publication March 8, 2006.
 GLYCEMIC INDEX AND LIVER STEATOSIS
TABLE 1
Maternal characteristics by ethnic group
Proportion with very
Age1
n (%)
Western (reference) 105 (29) 29.5 앐 4.73
Turkish 79 (22) 24.3 앐 4.74
Moroccan 69 (19) 26.4 앐 5.44
Other non-Western 105 (29) 26.3 앐 5.34
Total 358 (100) 26.8 앐 5.3
1
Means compared by using ANOVA and Dunnett’s test.
2
Means compared by using logistic regression.
3
x៮ 앐 SD (all such values).
4
P 울 0.001.
5
P 울 0.05.
6
P 울 0.01.
deficiency in an early stage of pregnancy in women of different
ethnic groups in The Hague.
SUBJECTS AND METHODS
Subjects
In June 2002, midwives whose practice was in a socioeco-
nomically deprived neighborhood in The Hague decided to add
the assessment of serum 25-hydroxyvitamin D [25(OH)D] to the
standard blood tests given to pregnant women (with health in-
surance) at their first antenatal visit. Serum 25(OH)D was mea-
sured with a radioimmunoassay (Diasorin, Stillwater, MN) by a
laboratory accredited by CCKL, the Dutch agency for laboratory
accreditation. This test assesses 25-hydroxyvitamin D2 and 25-
hydroxyvitamin D3 together, and, because the former is absent in
the Netherlands, this protocol is identical in the Netherlands with
the assessment of the latter. The intraassay and interassay CVs
were 6% to 7% and 9% to 11%, respectively. The lower detection
limit of the assay was 7 nmol/L.
Subsequently, the Municipal Health Service of The Hague
collected additional data from the files of the midwives (June
2002 through March 2004): date of blood sample (ie, the season
in which blood was drawn), self-reported ethnicity, age, postal
code, parity, smoking or alcohol or drug use, and infectious
diseases. Ethnicity is relevant in relation to type of skin. We
suspected that some women born in the Netherlands but with
foreign parents may have described themselves as being Dutch.
Therefore, we verified the subjects’ ethnicity by comparing it
with their family name at birth; we recoded the ethnicity in 15
cases. Women were categorized into 4 broad ethnic groups:
Western, Turkish, Moroccan, and other non-Western women.
The postal code was used to assign a deprivation score, which is
based on income, percentage of unemployed inhabitants, and the
quality of the housing; a high deprivation score is associated with
a low socioeconomic status.
Statistical analysis
We calculated the mean 25(OH)D values by replacing the
concentrations that were under the detection limit (ie,
쏝7 nmol/L) with concentrations of 3 nmol/L. Differences in
means between Western and non-Western ethnic groups were
351
high deprivation Tested January
score2 Primigravidae2 through March2
% % %
6 55 34
534 48 33
464 385 22
304 366 36
31 45 32
tested with ANOVA, and Dunnett’s test was used to correct for
multiple comparisons. Serum 25(OH)D concentrations were log
transformed because of lack of fit with the normal curve. Because
Downloaded from www.ajcn.org by on January 16, 2007
of unequal cell variances, this analysis was weighted by the
inverse variances of the subgroups (23). Differences in percent-
ages were tested by using logistic regression. All analyses were
performed by using SPSS software (version 12.0.1, SPSS Inc,
Chicago, IL).
RESULTS
In the period from June 2002 through March 2004, 762 women
came to the midwives’ practice in their 12th week of pregnancy.
Of these women, vitamin D concentrations for 358 (47%) were
found in the files.
Of these 358 women, 29% were of Western (including indig-
enous Dutch), 22% were of Turkish, and 19% were of Moroccan
origin (Table 1). Ages ranged from 17 to 42 y (x៮ : 26.8 y).
Thirty-one percent and 45% of the women lived in neighbor-
hoods with a very high and a high deprivation score, respectively.
Forty-five percent of the women were primigravidae, and 29%
were in their second pregnancy. Compared with the non-Western
women, the Western women were significantly older, signifi-
cantly fewer lived in a neighborhood with a very high deprivation
score, and a greater proportion were primigravidae (the last item
was not significant in comparison to Turkish women). No asso-
ciation was found between the season of blood sampling and the
ethnic group.
Serum 25(OH)D concentrations were significantly associated
with ethnic group (Table 2). The highest 25(OH)D concentra-
tions were found in the Western group, and the lowest were found
in the Turkish group. Replacement of concentrations that were
under the detection limit with values of either 0 or 6 nmol/L
resulted in almost identical means. In all non-Western groups,
most of the subjects (Turkish, 84%; Moroccan, 81%; other non-
Western women, 59%) had a vitamin D deficiency. Serum
25(OH)D was below the detection limit of 7 nmol/L in 22% of the
Turkish women.
The mean serum 25(OH)D concentrations did not differ signifi-
cantly between the seasons. We did not find a significant seasonal
variation even in the Western women, who had the lightest skin
[25(OH)D 쏝 25nmol/L: January–March, 6%; April–June, 10%;
352 VALTUENA ET AL
TABLE 2
Mean serum 25-hydroxyvitamin D [25(OH)D] concentrations in subjects and proportions of subjects with deficiency or with concentrations under the
detection limit
25(OH)D concentration1
Western (reference) (n ҃ 105) 52.7 앐 21.65
Turkish (n ҃ 79) 15.2 앐 12.16
Moroccan (n ҃ 69) 20.1 앐 13.56
Other non-Western (n ҃ 105) 26.3 앐 25.96
1
Means compared by using ANOVA and Dunnett’s test; vitamin D data were log transformed and weighted by inverse cell variances.
2
Deficiency ҃ 쏝 25 nmol 25(OH)D/L.
3
Means compared by using logistic regression.
4
Under the detection limit ҃ 쏝7 nmol 25(OH)D/L.
5
x៮ 앐 SD (all such values).
6
P 울 0.001.
7
P 울 0.05.
July–September, 4%; October–December, 12%). The relation be-
tween vitamin D and ethnicity was not confounded by age, season,
deprivation score of the neighborhood, parity, smoking or alcohol or
drug use, or infectious diseases.
DISCUSSION
Mean serum 25(OH)D concentrations in women of Turkish,
Moroccan, and other non-Western groups were significantly
lower than those in the Western women. In all non-Western
groups, most of the women had a vitamin D deficiency—ie,
serum 25(OH)D concentrations 쏝 25 nmol/L. This threshold is
the reference concentration of the analyzing laboratory and has
been debated in the literature (7). However, there is no consensus
about the appropriate threshold; higher thresholds have been
suggested (24 –26). These differences in 25(OH)D concentra-
tions between ethnic groups may be caused by differences in skin
type, skin covering (clothes), and the avoidance of direct sun
exposure. However, information on these variables was not
available.
The season of the blood sampling did not show a clear trend in
vitamin D concentrations. In the Netherlands (52° N), vitamin D
production in the skin takes place from April through September
(27). We would therefore presume the serum 25(OH)D concen-
trations in the July–September span to be the highest and those in
the January–March span to be the lowest. However, our results
do not support this presumption, even in the Western women—
ie, those with the lightest skin.
Vitamin D concentrations were available for 47% of 762 eli-
gible women. Possible reasons for this relatively low percentage
are that the midwives did not 1) add the vitamin D test to the
standard blood test, 2) receive the results from the laboratory, or
3) record the serum 25(OH)D concentration in the medical files.
We assume that this omission may have resulted in an underes-
timation of mean values. Even if, in a hypothetical situation, none
of the women with an unknown serum concentration of 25(OH)D
had a vitamin D deficiency, 25% of the total population would
still be vitamin D deficient, and such a situation would be a major
problem.
Some women came to the midwives’ practice during a late
stage of their pregnancy, had already undergone the standard
blood test given in another health-care setting, or both. These
women probably are at higher risk of a vitamin D deficiency
25(OH)D deficiency2,3 25(OH)D under the detection limit3,4
n (%) n (%)
8 (8) 1 (1)
66 (84)6 17 (22)6
56 (81)6 3 (4)
62 (59)6 9 (9)7
because most of them are non-Western. The inevitable exclusion
of these women will have caused selection bias that is opposite to
the 3 above-mentioned possible reasons. In total, 260 pregnant
women came later than the 12th wk of pregnancy, partly because
Downloaded from www.ajcn.org by on January 16, 2007
they came from a midwife or physician outside the participating
practice.
Some other studies have been conducted at a similar latitude
(20, 28 –30) and thus in a region with an intensity of sunlight
similar to that in the area in the current study. The overall con-
clusion in these studies was comparable: vitamin D deficiency is
common among ethnic minorities in the cities studied (ie, Cardiff
and London, United Kingdom), even early in pregnancy. Al-
though the first of these studies was published in 1981, the cur-
rent study indicates that the problem still has not been solved.
Dietary supplements may prevent vitamin D deficiency during
pregnancy. The Health Council of the Netherlands recommends
a higher amount of vitamin D for pregnant than for nonpregnant
women. Because of a lack of evidence, this recommendation is
not generally accepted (11, 15, 31). The current study shows,
irrespective of this discussion, that special attention should be
paid to non-Western pregnant women in the Netherlands. This
recommendation is supported by recent case histories of convul-
sion in the newborns of non-Western mothers in the Netherlands
(32). These convulsions were due to a vitamin D deficiency in the
mother during pregnancy.
If the pregnancy itself is not the cause of the vitamin D defi-
ciency, it can be said that (preventive) campaigns should aim at
all non-Western women, not only pregnant women. However,
pregnant women are more easily reachable because of their reg-
ular antenatal visits. In addition, the deficiency affects not only
the mother, because the vitamin D status of the (unborn) child is
dependent on the mother (33). There is no consensus about the
adequate amount of vitamin D supplementation to prevent or
cure a vitamin D deficiency (31, 34). A study by Cockburn et al
(35) found that a dose of 400 IU/d for 4 mo resulted in 25(OH)D
concentrations that were 3.8 nmol/L higher than baseline. How-
ever, the baseline concentrations in the population in the current
study were lower than those of subjects in the study by Cockburn
et al, and therefore a higher dose should be considered for our
subjects.
Our estimation of the percentage of vitamin D– deficient preg-
nant non-Western women is conservative. With thresholds 쏜 25
nmol/L, the percentage may rise to almost 100%. Although not
 GLYCEMIC INDEX AND LIVER STEATOSIS
all effects mentioned above are the proven result of a vitamin D
deficiency, enough evidence exists for us to consider a vitamin D
concentration 쏝 25 nmol/L as a deficiency. These deficiencies
should be diagnosed and cured, and therefore we recommend the
screening of all pregnant non-Western women for vitamin D
deficiency. The high prevalences found in this study, the size of
the population groups at risk, and the consequences of inaction
make this screening and treatment necessary.
We gratefully acknowledge the statistical assistance of DL Knol.
IMM, NSK, BJCM, IV, and JDW designed the study; IMM, NSK, and IV
collected the data; IMM and NSK analyzed the data; BJCM supervised the
analysis of the data; and all authors were involved in writing the manuscript.
None of the authors had a personal or financial conflict of interest.
REFERENCES
1. Clemens TL, Adams JS, Henderson SL, Holick MF. Increased skin
pigment reduces the capacity of skin to synthesise vitamin D3. Lancet
1982;1:74 – 6.
2. Harris SS, Dawson-Hughes B. Seasonal changes in plasma 25-
hydroxyvitamin D concentrations of young American black and white
women. Am J Clin Nutr 1998;67:1232– 6.
3. Malvy DJ, Guinot C, Preziosi P, et al. Relationship between vitamin D
status and skin phototype in general adult population. Photochem Pho-
tobiol 2000;71:466 –9.
4. Glerup H, Mikkelsen K, Poulsen L, et al. Commonly recommended daily
intake of vitamin D is not sufficient if sunlight exposure is limited.
J Intern Med 2000;247:260 – 8.
5. Grootjans-Geerts I, Wielders JP. Pilotonderzoek naar hypovitaminose D
bij ogenschijnlijk gezonde gesluierde Turkse vrouwen: ernstige vita-
mine D-deficiëntie bij 82%. (A pilot study of hypovitaminosis D in
apparently healthy, veiled Turkish women: severe vitamin D deficiency
in 82%). Ned Tijdschr Geneeskd 2002;146:1100 –1 (in Dutch).
6. Glerup H, Mikkelsen K, Poulsen L, et al. Hypovitaminosis D myopathy
without biochemical signs of osteomalacic bone involvement. Calcif
Tissue Int 2000;66:419 –24.
7. Lips P. Vitamin D deficiency and secondary hyperparathyroidism in the
elderly: consequences for bone loss and fractures and therapeutic impli-
cations. Endocr Rev 2001;22:477–501.
8. Specker BL. Do North American women need supplemental vitamin D
during pregnancy or lactation? Am J Clin Nutr 1994;59(suppl):484S–
90S.
9. Arden NK, Major P, Poole JR, et al. Size at birth, adult intestinal calcium
absorption and 1,25(OH)(2) vitamin D. Q J Med 2002;95:15–21.
10. Namgung R, Tsang RC. Bone in the pregnant mother and newborn at
birth. Clin Chim Acta 2003;333:1–11.
11. Specker B. Vitamin D requirements during pregnancy. Am J Clin Nutr
2004;80(suppl):1740S–7S.
12. McGrath J. Does ‘imprinting’ with low prenatal vitamin D contribute to
the risk of various adult disorders? Med Hypotheses 2001;56:367–71.
13. Barker DJP. Mothers, babies and health in later life. 2nd ed. Edinburgh,
United Kingdom: Churchill Livingstone, 1998.
14. Health Council of the Netherlands. Voedingsnormen: calcium, vitamine
D, thiamine, riboflavine, niacine, pantotheenzuur en biotine. (Dietary
reference intakes: calcium, vitamin D, thiamin, riboflavin, niacin, pan-
tothenic acid, and biotin.) The Hague, Netherlands: Health Council of
the Netherlands, 2000 (in Dutch).
353
15. Wiersma TJ, Daemers DO, Steegers EA, Flikweert S. Onterechte aan-
beveling voor extra vitamine D bij zwangeren en zogenden. (Unfounded
recommendations for vitamin D supplementation in pregnant and breast-
feeding women. ) Ned Tijdschr Geneeskd 2001;145:1700 –1 (in Dutch).
16. Heckmatt JZ, Peacock M, Davies AE, McMurray J, Isherwood DM.
Plasma 25-hydroxyvitamin D in pregnant Asian women and their babies.
Lancet 1979;2:546 – 8.
17. Bassir M, Laborie S, Lapillonne A, Claris O, Chappuis MC, Salle BL.
Vitamin D deficiency in Iranian mothers and their neonates: a pilot study.
Acta Paediatr 2001;90:577–9.
18. Grover SR, Morley R. Vitamin D deficiency in veiled or dark-skinned
pregnant women. Med J Aust 2001;175:251–2.
19. Andiran N, Yordam N, Ozon A. Risk factors for vitamin D deficiency in
breast-fed newborns and their mothers. Nutrition 2002;18:47–50.
20. Datta S, Alfaham M, Davies DP, et al. Vitamin D deficiency in pregnant
women from a non-European ethnic minority population—an interven-
tional study. Br J Obstet Gynaecol 2002;109:905– 8.
21. Pehlivan I, Hatun S, Aydogan M, Babaoglu K, Gokalp AS. Maternal
vitamin D deficiency and vitamin D supplementation in healthy infants.
Turk J Pediatr 2003;45:315–20.
22. Sachan A, Gupta R, Das V, Agarwal A, Awasthi PK, Bhatia V. High
prevalence of vitamin D deficiency among pregnant women and their
newborns in northern India. Am J Clin Nutr 2005;81:1060 – 4.
23. Neter J, Kutner MH, Nachtsheim CJ, Wasserman W. Applied linear
statistical models. 4th ed. Burr Ridge, IL: Richard D Irwin, 1996.
24. Malabanan A, Veronikis IE, Holick MF. Redefining vitamin D insuffi-
Downloaded from www.ajcn.org by on January 16, 2007
ciency. Lancet 1998;351:805– 6.
25. Dawson-Hughes B, Heaney RP, Holick MF, Lips P, Meunier PJ, Vieth
R. Estimates of optimal vitamin D status. Osteoporos Int
2005;16:713– 6.
26. Hollis BW. Circulating 25-hydroxyvitamin D levels indicative of vita-
min D sufficiency: implications for establishing a new effective dietary
intake recommendation for vitamin D. J Nutr 2005;135:317–22.
27. Webb AR, Kline L, Holick MF. Influence of season and latitude on the
cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston
and Edmonton will not promote vitamin D3 synthesis in human skin.
J Clin Endocrinol Metab 1988;67:373– 8.
28. Brooke OG, Brown IR, Cleeve HJ, Sood A. Observations on the vitamin
D state of pregnant Asian women in London. Br J Obstet Gynaecol
1981;88:18 –26.
29. Okonofua F, Menon RK, Houlder S, et al. Calcium, vitamin D and
parathyroid hormone relationships in pregnant Caucasian and Asian
women and their neonates. Ann Clin Biochem 1987;24:22– 8.
30. Alfaham M, Woodhead S, Pask G, Davies D. Vitamin D deficiency: a
concern in pregnant Asian women. Br J Nutr 1995;73:881–7.
31. Hollis BW, Wagner CL. Assessment of dietary vitamin D requirements
during pregnancy and lactation. Am J Clin Nutr 2004;79:717–26.
32. Dijkstra SH, Arpaci G, Huijsman WA, Boot AM, van den Akker EL.
Convulsies bij allochtone pasgeborenen door hypovitaminose D bij de
moeder. (Seizures in foreign newborns due to maternal vitamin D defi-
ciency. ) Ned Tijdschr Geneeskd 2005;149:257– 60 (in Dutch).
33. Salle BL, Delvin EE, Lapillonne A, Bishop NJ, Glorieux FH. Perinatal
metabolism of vitamin D. Am J Clin Nutr 2000;71(suppl):1317S–24S.
34. Pawley N, Bishop NJ. Prenatal and infant predictors of bone health: the
influence of vitamin D. Am J Clin Nutr 2004;80(suppl):1748S–51S.
35. Cockburn F, Belton NR, Purvis RJ, et al. Maternal vitamin D intake and
mineral metabolism in mothers and their newborn infants. Br Med J
1980;281:11– 4.