Medical Hypotheses (2008) 71, 266–269

http://intl.elsevierhealth.com/journals/mehy

Maternal vitamin D in pregnancy may influence not

only offspring bone mass but other aspects of
musculoskeletal health and adiposity
Julie A. Pasco a,*, John D. Wark b, John B. Carlin c,d,
Anne-Louise Ponsonby d, Peter J. Vuillermin e, Ruth Morley c,d

a
Epidemiology and Biostatistics Unit, Department of Clinical and Biomedical Sciences: Barwon Health,
The University of Melbourne, Australia
b
Royal Melbourne Hospital Department of Medicine, The University of Melbourne, Australia
c
Department of Paediatrics, The University of Melbourne, Australia
d
Murdoch Childrens Research Institute, Australia
e
Department of Paediatrics, Barwon Health, Australia

Received 22 January 2008; accepted 31 January 2008

Summary Osteoporotic fractures, falls and obesity are major health problems in developed nations. Evidence
suggests that there are antenatal factors predisposing to these conditions. Data are emerging from Australia and
elsewhere to suggest that maternal vitamin D status in pregnancy affects intrauterine skeletal mineralisation and
skeletal growth together with muscle development and adiposity. Given that low levels of vitamin D have been
documented in many urbanised populations, including those in countries with abundant sunlight, an important issue for
public health is whether maternal vitamin D insufficiency during pregnancy has adverse effects on offspring health. The
developing fetus may be exposed to low levels of vitamin D during critical phases of development as a result of
maternal hypovitaminosis D. We hypothesise that this may have adverse effects on offspring musculoskeletal health
and other aspects of body composition. Further research focused on the implications of poor gestational vitamin D
nutrition is warranted as these developmental effects are likely to have a sustained influence on health during
childhood and in adult life. We suggest that there is a clear rationale for randomised clinical trials to assess the
potential benefits and harmful effects of vitamin D supplementation during pregnancy.
c 2008 Elsevier Ltd. All rights reserved.

* Corresponding author. Address: Epidemiology and Biostatis-
tics Unit, Department of Clinical and Biomedical Sciences:
Barwon Health, The University of Melbourne, P.O. Box 281,
Geelong VIC 3220, Australia. Tel.: +61 3 5226 7393; fax: +61 3
5246 5165.
E-mail address: juliep@barwonhealth.org.au (J.A. Pasco).
Vitamin D
Vitamin D status, measured as the circulating 25-
hydroxyvitamin D (25OHD) level, is a key determi-
nant of production of 1,25-dihydroxyvitamin D
(1,25(OH)2D), the secosteroid hormone required
for normal bone growth and mineralisation [1],


0306-9877/$ - see front matter c 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.mehy.2008.01.033
Maternal vitamin D in pregnancy may influence not only offspring
and for increasing the number and size of muscle
fibres [2].
Vitamin D does not naturally occur in the major-
ity of unfortified foods [3]; hence, in many coun-
tries vitamin D is derived predominantly from sun
exposure [4]. Personal sun exposure may have de-
creased in westernised communities since the
1960s for a number of reasons. These include an
increasingly indoor lifestyle with indoor electronic
leisure activities, concerns about safety, urban de-
sign and sun avoidance campaigns for skin cancer
prevention. Not surprisingly, low levels of vitamin
D have been documented in many populations
worldwide, including countries with abundant sun-
light [5–9]. A significant number of women in Aus-
tralia, including those of reproductive age, have
low serum 25OHD levels [5,7,10]. Maternal vitamin
D insufficiency is a cause for concern not only for
the mothers, but also because it exposes the off-
spring to insufficiency during potentially critical
early phases of development both in utero and
postnatally.
Vitamin D deficiency in infancy or childhood is
known to affect bone health and muscle function,
with affected individuals having abnormal bone
turnover together with rickets and myopathy in
severe deficiency [11]. An important issue for
public health is whether maternal vitamin D
insufficiency during gestation has a long-term or
even permanent adverse effect on musculoskele-
tal and other aspects of body composition in
the offspring.
Musculoskeletal health
Extant literature suggests that the risk of osteopo-
rosis and consequent fragility fractures in adult life
might be programmed by environmental influences
during gestation [12]. There are also data to sug-
gest that maternal vitamin D status during preg-
nancy affects intrauterine skeletal mineralisation
[13] and skeletal growth in children [14]. Maternal
veiling in pregnancy, a surrogate for low vitamin D
levels, has been associated with reduced bone
mass among adolescent boys [15]. In a longitudinal
study of mothers and their offspring in the UK, re-
duced maternal vitamin D in late pregnancy was
associated with reduced whole body and lumbar
spine bone mineral content in the children at age
nine years [14]. Exposure to ultraviolet B (UVB)
radiation and maternal vitamin D supplementation,
both during late pregnancy, predicted maternal
vitamin D status and bone mass in the offspring at
age nine.
267
In an Australian study, Morley et al. [8] mea-
sured maternal vitamin D status at approximately
11 weeks and at 28–32 weeks gestation and ob-
tained anthropometric measurements in the off-
spring at birth and at one year. Babies born to
women with low 25OHD levels at the beginning of
the third trimester (defined as <28 nmol/L) had
4.3 mm smaller (95% confidence interval 7.3,
1.3) knee–heel length at birth, a marker of im-
paired long bone growth in utero. Gestation length
was 0.7 wk ( 1.3, 0.1) shorter and the difference
in knee-heel length was reduced to 2.7 mm
( 5.4, 0.1) after adjustment for gestation length,
suggesting that this growth deficit was partly med-
iated via an effect of vitamin D on gestation length.
Low maternal 25OHD was also associated with re-
duced offspring mid-upper arm and calf circumfer-
ence at birth, with no evidence of a difference in
triceps skinfold thickness. These findings suggest
that infants of mothers with low 25OHD in late
pregnancy may have decreased limb lean tissue.
There was also weak evidence of increased
subscapular subcutaneous fat deposition in the
deficient group, suggesting the possibility of in-
creased central deposition of fat.
There are seasonal periodicity data relating
month-of-birth to adult height [16] and to the prev-
alence of musculoskeletal disorders [17]. A Norwe-
gian rehabilitation centre for musculoskeletal
disorders reported peak numbers of records for pa-
tients who were born in mid-summer [17]. This
complements data showing that, compared to win-
ter-born infants, those born in summer have lower
radial bone mineral content [18]. These patterns
may relate to vitamin D in pregnancy, supporting
the notion that fetal exposure to low vitamin D in
the second trimester is related to poorer skeletal
outcomes.
Vitamin D deficiency in elderly adults has also
been identified as an independent predictor of
falls, contributing to the pathogenesis of osteopo-
rotic fractures [19] and, in the Iowa Women’s
Health Study, vitamin D supplementation was asso-
ciated with a reduced risk of the onset of rheuma-
toid arthritis [20]. In osteomalacia, a metabolic
myopathy has been observed, accompanied by gait
disturbances and difficulties in rising from a chair.
However, we have to rely largely on data from ani-
mal models to link maternal vitamin D status and
fetal muscle development. A study tracing 3H-la-
belled vitamin D injected into mother rats showed
that 25OHD was transferred to the fetus and stored
predominantly in fetal muscle tissue [21]. Other
animal studies have demonstrated stimulatory ef-
fects of vitamin D on the growth and differentia-
tion of cultured chick myoblasts [22] and vitamin
268
D-promotion of myogenesis, as indicated by an in-
crease in specific muscle differentiation markers
and myosin expression [23]. These studies support
a role for vitamin D in embryonic muscle growth
and maturation. As previously stated, Morley
et al. [8] report data to suggest that maternal vita-
min D status during pregnancy affects intrauterine
lean tissue development in human offspring, but
this appears to be the only published study to have
addressed this issue.
Adiposity
There is evidence from two studies that adult body
mass index and the prevalence of obesity vary as a
function of month of birth [24,25]. Greater adipos-
ity was found for men and women born in winter–
spring, possibly reflecting fetal exposure to low
vitamin D during the second or third trimester of
pregnancy.
Vitamin D deficiency is also emerging as a risk
factor for the metabolic syndrome in adults [26].
The evidence supports an inverse relationship be-
tween serum 25OHD and components of the
metabolic syndrome, including blood glucose con-
centration, insulin resistance, dyslipidemia, raised
blood pressure and abdominal obesity [26].
Although it may be assumed that the cross-sec-
tional association observed between low serum
25OHD and obesity in children [27] reflects, at least
in part, storage of vitamin D (which is fat soluble)
in adipose tissue, the issue of causality has not
been investigated. In vitro studies show that the
highly active form of vitamin D, 1,25(OH)2D3, ex-
erts a coordinated control over lipogenesis and lyp-
olysis [28]. Given current concerns about childhood
obesity and the increasing prevalence of vitamin D
deficiency with urbanisation, it is important to ex-
plore the hypothesis that maternal vitamin D level
may affect later body size and composition.
Conclusion
There is an emerging body of evidence to suggest
that intrauterine vitamin D insufficiency may also
be associated with later development of autoim-
mune and cardiovascular diseases, type I diabetes,
schizophrenia, seasonal affective disorder and
some cancers [7], but we have focussed on the
hypothesis that maternal vitamin D insufficiency
during pregnancy affects bone mass and other as-
pects of musculoskeletal development and adipos-
ity in the offspring. We emphasise that adequate
Pasco et al.
maternal vitamin D nutrition should be recognised
as important to optimise offspring growth and
development.
Recommendations for increased exposure to
sunlight or routine vitamin D supplementation dur-
ing pregnancy remain contentious issues [29–31] of
large potential public health importance and war-
rant further research. Future randomised clinical
trials of vitamin D supplementation for women dur-
ing pregnancy are anticipated. These studies
should circumvent potential confounding such as
coincident seasonal variations in maternal intakes
of other nutrients during pregnancy that may also
influence fetal development [32].
References
[1] DeLuca HF, Zierold C. Mechanisms and functions of vitamin
D. Nutr Rev 1998;56:S4–S10 [Discussion S 54–75].
[2] Sorensen OH, Lund B, Saltin B, et al. Myopathy in bone loss
of ageing: improvement by treatment with 1 alpha-hydrox-
ycholecalciferol and calcium. Clin Sci (London) 1979;56:
157–61.
[3] Lamberg-Allardt C. Vitamin D in foods and as supplements.
Prog Biophys Mol Biol 2006;92:33–8.
[4] Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D
concentrations, and safety. Am J Clin Nutr 1999;69:
842–56.
[5] Pasco JA, Henry MJ, Nicholson GC, Sanders KM, Kotowicz
MA. Vitamin D status of women in The Geelong Osteoporosis
Study: association with diet and casual exposure to
sunlight. Med J Aust 2001;175:401–4015.
[6] Nesby-O’Dell S, Scanlon KS, Cogswell ME, et al. Hypovita-
minosis D prevalence and determinants among African
American and white women of reproductive age: third
national health and nutrition examination survey, 1988–
1994. Am J Clin Nutr 2002;76:187–92.
[7] Working Group of the Australian and New Zealand Bone and
Mineral Society; Endocrine Society of Australia; Osteopo-
rosis Australia. Vitamin D and adult bone health in Australia
and New Zealand: a position statement. Med J Aust
2005;182:281–5.
[8] Morley R, Carlin JB, Pasco JA, Wark JD. Maternal 25-
hydroxyvitamin D and parathyroid hormone concentrations
and offspring birth size. J Clin Endocrinol Metab 2006;91:
906–12.
[9] Binkley N, Novotny R, Krueger D, et al. Low vitamin D
status despite abundant sun exposure. J Clin Endocrinol
Metab 2007;92:2130–5.
[10] Morley R, Grover SR, Pasco JA, Nicholson GC, McGrath J,
Vieth R. Vitamin D in pregnant women. Arch Dis Child
2002;Letter 5: March.
[11] Munns C, Zacharin MR, Rodda CP, et al. Prevention and
treatment of infant and childhood vitamin D deficiency in
Australia and New Zealand: a consensus statement. Med J
Aust 2006;185:268–72.
[12] Javaid MK, Cooper C. Prenatal and childhood influences on
osteoporosis. Best Pract Res Clin Endocrinol Metab 2002;16:
349–67.
[13] Gale CR, Martyn CN, Kellingray S, Eastell R, Cooper C.
Intrauterine programming of adult body composition. J Clin
Endocrinol Metab 2001;86:267–72.
Maternal vitamin D in pregnancy may influence not only offspring
[14] Javaid MK, Crozier SR, Harvey NC, et al. Maternal
vitamin D status during pregnancy and childhood bone
mass at age 9 years: a longitudinal study. Lancet
2006;367:36–43.
[15] Nabulsi M, Mahfoud Z, Maalouf J, Arabi A, Fuleihan GE.
Impact of maternal veiling during pregnancy and socioeco-
nomic status on offspring’s musculoskeletal health. Osteo-
poros Int 2007; August 29 [Epub ahead of print].
[16] Fitt AB. The heights and weights of men according to month
of birth. Human Biol 1955;27:138–42.
[17] Fonnebo V. Month of birth and prevalence of musculoskel-
etal diseases later in life. Lancet 1987;1:739–40.
[18] Namgung R, Mimouni F, Campaigne BN, Ho ML, Tsang RC.
Low bone mineral content in summer-born compared with
winter-born infants. J Pediatr Gastroenterol Nutr 1992;15:
285–8.
[19] Flicker L, MacInnis RJ, Stein MS, et al. Should older people in
residential care receive vitamin D to prevent falls? Results of
a randomized trial. J Am Geriatr Soc 2005;53:1881–8.
[20] Merlino LA, Curtis J, Mikuls TR, Cerhan JR, Criswell LA, Saag
KG. Vitamin D intake is inversely associated with rheuma-
toid arthritis: results from the Iowa Women’s Health Study.
Arthritis Rheum 2004;50:72–7.
[21] Clements MR, Fraser DR. Vitamin D supply to the rat fetus
and neonate. J Clin Invest 1988;81:1768–73.
[22] Giuliani DL, Boland RL. Effects of vitamin D3 metabolites on
calcium fluxes in intact chicken skeletal muscle and
myoblasts cultured in vitro. Calcif Tissue Int 1984;36:
200–5.
[23] Capiati DA, Tellez-Inon MT, Boland RL. Participation of
protein kinase C alpha in 1,25-dihydroxy vitamin D3
Available online at www.sciencedirect.com
269
regulation of chick myoblast proliferation and differentia-
tion. Mol Cell Endocrinol 1999;153:39–45.
[24] Levitan RD, Masellis M, Lam RW, et al. A birth-season/
DRD4 gene interaction predicts weight gain and obesity in
women with seasonal affective disorder: a seasonal thrifty
phenotype hypothesis. Neuropsychopharmacology 2006;31:
2498–503.
[25] Phillips DI, Young JB. Birth weight, climate at birth and the
risk of obesity in adult life. Int J Obes Relat Metab Disord
2000;24:281–7.
[26] Martini LA, Wood RJ. Vitamin D status and the metabolic
syndrome. Nutr Rev 2006;64:479–86.
[27] Rockell JE, Green TJ, Skeaff CM, et al. Season and
ethnicity are determinants of serum 25-hydroxyvitamin D
concentrations in New Zealand children aged 5–14 y. J Nutr
2005;135:2602–8.
[28] Shi H, Norman AW, Okamura WH, Sen A, Zemel MB.
1alpha,25-Dihydroxyvitamin D3 modulates human adipo-
cyte metabolism via nongenomic action. FASEB J 2001;15:
2751–3.
[29] Mahomed K, Gulmezoglu AM. Vitamin D supplementation in
pregnancy. Cochrane Database Syst Rev 2000 [CD000228].
[30] Moy R, Shaw N, Mather I. Vitamin D supplementation in
pregnancy. Lancet 2004;363:574.
[31] Ebeling P, Eisman J, Flicker L, et al. Recommendations
from the vitamin D and calcium forum. Med Today 2005;6:
43–50.
[32] Watson PE, McDonald BW. Seasonal variation of nutrient
intake in pregnancy: effects on infant measures and
possible influence on diseases related to season of birth.
Eur J Clin Nutr 2007;61:1271–80.