N U TR IT ION RE S EA R CH 6 3 ( 20 1 9 ) 1– 2 0

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Review Article

Maternal risk factors and newborn infant vitamin

D status: a scoping literature review

Olusola F. Sotunde 1 , Alexandra Laliberte 1 , Hope A. Weiler⁎

School of Human Nutrition, McGill University Ste Anne de Bellevue, Québec, Canada H9X 3V9

ARTI CLE I NFO A BS TRACT

Article history: Low vitamin D (VitD) status is common among newborn infants, more so in temperate latitudes with
Received 18 September 2018 evidence that maternal VitD deficiency is a major risk factor given that the neonate relies solely on
Revised 19 November 2018 maternal-fetal transfer of VitD. This scoping review was conducted to provide an overview of the
Accepted 30 November 2018 latest evidence from studies regarding the impact of maternal risk factors on infant 25-
hydryoxyvitamin D [25(OH)D] concentrations with a focus on studies in Canada and the United
Keywords: States. Several maternal risk factors that contribute to low maternal-fetal 25(OH)D concentrations
Pregnancy have been reported over many decades, but no clear pattern has been established for multiethnic
Neonates populations. For example, darker skin pigmentation and ethnicity are common risk factors for low
Vitamin D status VitD status. Studies in predominantly white women showed that supplementation of VitD during
Risk factors pregnancy causes significant increases in maternal serum 25(OH)D which often improves cord
serum 25(OH)D values. In addition, VitD recommendations by health care professionals and
adherence to supplementation by pregnant women appear to positively influence maternal and
infant 25(OH)D concentrations. Conversely, winter season, obesity, lower socioeconomic status
including lifestyle factors (smoking), and use of medication pose risk for lower maternal-fetal
transfer of VitD. However, there is still a dearth of pertinent data on the relationship between some of
the maternal risk factors and newborn 25(OH)D concentrations, for instance, relationships between
gestational diabetes and neonatal VitD status. Additional research is required to determine if the
same target for 25(OH)D concentrations applies for pregnant women, neonates, and infants.
Crown Copyright © 2018 Published by Elsevier Inc. All rights reserved.

Article Outline

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
2. Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
3. Vitamin D metabolism in fetus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
3.1. Consequences of vitamin D deficiency during pregnancy and infancy . . . . . . . . . . . . . . . . . . . . . . . . . 3

Abbreviations: 1,25(OH)2D, 1,25-dihydroxyvitamin D; 25(OH)D, 25-hydroxyvitamin D; BMI, body mass index; DRI, Dietary Reference
Intake; GDM, gestational diabetes mellitus; IOM, Institute of Medicine; MIREC, Maternal-Infant Research on Environmental Chemicals;
NHANES, National Health and Nutrition Examination Survey; PIH, pregnancy-induced hypertension; RDA, Recommended Dietary
Allowance; SES, socioeconomic status; VDBP, vitamin D–binding protein; VitD, vitamin D.
⁎ Corresponding author.
E-mail addresses: olusola.sotunde@mcgill.ca (O.F. Sotunde), alexandra.laliberte@mail.mcgill.ca (A. Laliberte), hope.weiler@mcgill.ca
(H.A. Weiler).
1
Authors contributed equally.

https://doi.org/10.1016/j.nutres.2018.11.011
0271-5317/Crown Copyright © 2018 Published by Elsevier Inc. All rights reserved.
2 N U TR IT ION RE S EA R CH 63 ( 20 1 9 ) 1 – 2 0

4. Maternal influence and risk factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

4.1. Recommendations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
4.1.1. Definitions and ranges of vitamin D . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
4.1.2. Dietary recommendations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
4.2. Dietary intake and use of supplements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
4.2.1. Dietary intake . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
4.2.2. Use of supplements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
4.2.3. Population statistics on vitamin D supplementation of infants . . . . . . . . . . . . . . . . . . . . . . 12
4.3. Maternal vitamin D status . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
4.4. Sunlight exposure, ethnicity, and skin pigmentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
4.5. Seasonal variations and clothing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
4.6. Professional opinion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
4.7. SES and education . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
4.8. Maternal morbidities/pregnancy complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
4.8.1. Body mass index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
4.8.2. Hypertensive disease in pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
4.8.3. Gestational diabetes mellitus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
4.9. Lifestyle factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
4.9.1. Smoking status. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
4.9.2. Use of medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
5. Knowledge gaps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
6. Summary and conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
Acknowledgment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

1. Introduction the production of 1,25(OH)2D during pregnancy, an approxi-

As a result of high prevalence rates of vitamin D (VitD) deficiency
among children and the persistent incidence of rickets, several
upward revisions of recommended daily intakes of VitD have
occurred [1,2]. The National Academy of Science, formerly known
as the Institute of Medicine (IOM), updated the VitD Recommended
Dietary Allowance (RDA) in 2011 for pregnant and lactating
women to 600 IU. For infants, the Adequate Intake was increased
to 400 IU to achieve and maintain VitD serum/plasma concen-
tration of at least 40 nmol/L of 25-hydroxyvitamin D [25(OH)D] [2]
and to prevent VitD deficiency and rickets [3]. VitD is of key
importance for calcium and bone metabolism during pregnancy
and lactation for both the mother and neonate(s). VitD also has
nonskeletal effects, including its role in the development of
healthy body composition [4-6] and improved birth outcomes [7].
During pregnancy, VitD metabolism and calcium homoeostasis
are regulated by many factors, including prolactin, placental
lactogen, osteoprotegerin, calcitonin, and estrogen [8,9]. Be-
cause maternal-fetal transfer of VitD is the only source for the
fetus, a brief review of maternal physiology is warranted.
Significant changes occur during pregnancy, starting with the
enhanced conversion of 25(OH)D to 1,25-dihydroxyvitamin D
[1,25(OH)2D]. Free 1,25(OH)2D concentrations increase as does
vitamin D–binding protein (VDBP) [10]. In the first trimester,
maternal concentrations of 1,25(OH)2D double and continue to
increase to 3-fold the prepregnancy concentration [10]. This
increase in 1,25(OH)2D contributes to the increase in intestinal
calcium absorption to meet the fetal demand for mineralization
of the skeleton [11]. An increase in VDBP observed in pregnancy
is equally significant, as one of the major roles of VDBP is to
bind and transport 25(OH)D and 1,25(OH)2D [12]. To optimize
mate circulating 25(OH)D precursor concentration of 100 nmol/
L is reportedly required [13].
VitD status is not routinely tested in pregnant women or
neonates because of its relatively high cost to health care.
Two pregnancy cohorts in Canada measured VitD status
in infants, suggesting that approximately 24.4% of infants are
born with a serum 25(OH)D concentration below 50 nmol/L
[14], and 80% infants are born with 25(OH)D concentration
below 75 nmol/L [15]. In a US cohort study, 45.6% of black and
9.7% of white infants are born with 25(OH)D below 37.5 nmol/L
using the 1997 IOM definition of VitD deficiency at the time of
reporting [16]. According to the Canadian Paediatric Society,
infants are at higher risk of VitD deficiency [<25 nmol/L of 25
(OH)D] if they are breast-fed, their mother has low VitD
status, their skin pigmentation is darker, and they live in
northern communities or are Aboriginal [17,18]. However, as
maternal 25(OH)D concentration is not routinely known and
other previously identified risk factors are not fully eluci-
dated, some of the population at risk of low or deficient 25
(OH)D concentrations at birth might be unidentified. There-
fore, the main objective of this literature review is to shed
light on the various maternal factors that could impact infant
25(OH)D concentrations.
2. Approach
Literature searches were conducted using PubMed and Google
Scholar databases for studies published before July 31, 2018.
The search terms included VitD, 25-hydroxyvitamin D, 25(OH)D,
umbilical cord serum 25(OH)D, VitD deficiency, hypovitaminosis D,
 N U TR IT ION RE S EA R CH 6 3 ( 20 1 9 ) 1– 2 0
VitD synthesis, prenatal VitD exposure, Canada, United States,
pregnancy, fetus, infant, birthweight, infant length, rickets, bone
quality, supplementation, mother-newborn pair, maternal risk
factors, maternal VitD status, obesity, smoking, skin pigmentation,
ethnicity, SES, education, dietary intake, pre-pregnancy body mass
index (BMI), sun exposure and screening tool. Articles retrieved
were evaluated on their relevance to the topic of this review, and
studies on nonhumans, those that used nonblood measures of 25
(OH)D (placenta or amniotic fluid), and those published in non-
English languages were excluded. Additional relevant studies
were included as identified from reference lists of primary
papers, review articles, and meta-analyses.
3. Vitamin D metabolism in fetus
Fetal VitD requirements are higher in the latter half of
pregnancy because of bone growth and ossification and to
build VitD stores for use postnatally. Placental transfer of 25
(OH)D is the major source of VitD for the developing fetus [19]
and crosses the hemochorial human placenta as suggested by
positive correlations between cord blood 25(OH)D and mater-
nal concentrations [20,21]. Therefore, sufficient maternal VitD
stores are important to meet their own needs and those of the
fetus [18]. Nevertheless, limited research is available regard-
ing fetal development and VitD metabolism.
3.1. Consequences of vitamin D deficiency during pregnancy
and infancy
VitD insufficiency has been associated with impaired growth
and bone development [22]. A cohort study of mother-
offspring pairs showed the adverse effect of low maternal
VitD status on fetal femoral development, which is evident as
splaying of the distal metaphysis of the femur and seen as
early as 19 weeks of gestation [22]. Less optimal intrauterine
bone growth may be explained by impaired placental calcium
exchange, which might be mediated by parathyroid-related
hormone peptide [23]. Congenital rickets is an example of
extremely adverse effect of low VitD stores in utero, resulting
in defective bone modeling [24] and a higher incidence of
neonatal morbidity [25]. Attributable to VitD deficiency,
postnatal rickets can be prevented with adequate nutritional
intake of VitD. Unfortunately, subclinical rickets is difficult to
detect early after birth, whereas the peak manifestation of
fulminant rickets is typically observed between 3 and
18 months of age [24].
In Canada, the estimated annual incidence rate of rickets
is 2.9 cases per 100 000 occurring between 2 weeks and
6 years of age. The highest rates of incidence occur among
infants with darker skin pigmentation, from northern com-
munities, and with a lack of VitD supplementation [26]. The
US Centers for Disease Control and Prevention in 2001
identified 6 cases of nutritional rickets in infants who were
breast-fed for over 6 months without receiving VitD supple-
ments [27]. A review of nutritional rickets case reports among
US children <18 years identified 166 cases of rickets in 22
published studies between 1986 and 2003 [28]. Most (83%) of
the children were African Americans and 96% were breast-
3
fed, with only 5% of the breast-fed children given VitD
supplementation during breast-feeding [28].
Furthermore, proxies for infant health have been reported
to be influenced by maternal 25(OH)D concentrations [29-31].
A post hoc analysis of 2 pregnancy supplementation trials
reported a 59% lower risk of preterm birth in women with 25
(OH)D concentrations ≥100 nmol/L compared to pregnant
women with ≤50 nmol/L (P = .02) [32]. Based on this finding,
a study of 1064 women was carried out at the Medical
University of South Carolina, USA, to investigate if a similar
result would be observed in their general obstetrical popula-
tion [33]. The study reported a 62% reduction in risk of
preterm birth in women with 25(OH)D ≥ 100 nmol/L com-
pared to those with ≤50 nmol/L (P < .0001) [33]. Robinson et al
[29] found a positive correlation between maternal 25(OH)D
concentrations and birthweight centiles. This finding corrob-
orates other studies including meta-analyses, which reported
a higher risk of having a small-for-gestational-age infant for
women with VitD deficiency [30,31], whereas others observed
that mean birthweight in infants of deficient mothers was
200 g lower than neonates born to women with sufficient VitD
status [34]. Furthermore, a multicentered US cohort study
reported that infants with maternal 25(OH)D < 30 nmol/L
were smaller at birth compared to infants with maternal 25
(OH)D ≥ 30 nmol/L [35]. In contrast, an earlier Canadian study
found that VitD-deficient [25(OH)D < 27.5 nmol/L] infants
were heavier and longer but had lower whole-body bone
mineral content relative to body weight compared to those
with higher concentrations, suggesting inadequate support
for bone mineralization when deficient [36]. Wheeze and
asthma in the offspring have also been reported as outcomes
associated with low VitD intake during pregnancy [37-39]. The
Vitamin D Antenatal Asthma Reduction Trial reported a
significantly decreased risk of asthma/recurrent wheeze in
children at 3 years of age for every 12.5-nmol/L increase in
maternal 25(OH)D (adjusted odds ratio [OR], 0.92; 95% confi-
dence interval [CI], 0.85-0.99; P = .02) [39]. Consequently, VitD
deficiency during pregnancy is recognized for its immediate
and long-term implications to health of the offspring. Few
studies exist on the prevalence of low VitD status in neonates
in Canada and United States [14-16,36,40-42] (Fig. 1).
4. Maternal influence and risk factors
Fetal health is related to the ability of the mother to provide
adequate nutrients to their developing child [43], and nutri-
tional status of women before and/or during pregnancy can
significantly influence maternal-fetal outcomes [44,45]. Sev-
eral factors have been reported to influence VitD production
and stores in adults.
4.1. Recommendations
4.1.1. Definitions and ranges of vitamin D
Serum 25(OH)D concentration is considered to be the best
indicator of VitD status because it reflects the exogenous VitD
input from the diet and supplements plus endogenous
production [46]. Lack of consensus and definitions about
describing VitD status has generated various terminologies and
4 N U TR IT ION RE S EA R CH 63 ( 20 1 9 ) 1 – 2 0
Fig. 1 – Prevalence of low vitamin D status in neonates in Canada and United States. Data to create this illustration for different regions
of Canada and the United States are indicated in the reference number in brackets from the literature cited in this review.
ranges that have created challenges in this field of research [47].
The different threshold levels used in different regions increase
the difficulty of comparing results [48]. Despite the variable
definitions over time, the value of 50 nmol/L is now dominant in
many recommendations (Table 1). For example, the IOM defined
VitD sufficiency as concentrations of serum 25(OH)D ≥ 50 nmol/L
[3], but others reported that the target should be 75 nmol/L
[49,50]. A study on VitD status of infants showed that 50 nmol/L
was enough for bone health [51], but the Endocrine Society sets
the target at 75 nmol/L to maximize bone health and muscle
function [52]. At 75 nmol/L, it was also found to be associated
with fat mass and lean mass, suggesting that this concentration
may be important for leaner body composition during infancy [4].
The Canadian Paediatric Society defined VitD deficiency as
<25 nmol/L [18], whereas the IOM, Health Canada, and Endocrine
Society state that infants are at risk of VitD deficiency at serum 25
(OH)D < 30 nmol/L [3,46,52].
4.1.2. Dietary recommendations
Given the evidence on the role of VitD on maternal-fetal
outcomes, specific recommendations have emerged to main-
tain maternal and infant VitD status within healthy target
ranges. In the absence of UVB exposure, maternal VitD status
is entirely dependent on storage pools and all sources of
exogenous VitD, be it from natural food sources, fortified
foods, or supplements. VitD from endogenous and exogenous
sources is a prohormone which can be stored for later use [3].
According to food fortification policy, VitD remains a vitamin, and
it is a topic of policy revisions to ensure that food supply better
meets the needs of the population [46]. For the United States and
Canada, the 2011 Dietary Reference Intakes (DRIs) for VitD by the
IOM were set considering minimal sunlight exposure and for the
purpose of maintaining bone health [46]. In the updated DRIs of
2011, the Committee generated an RDA for pregnant and lactating
women and Adequate Intakes for infants [3].
Health Canada recommends consumption of 2 cups of
fluid milk or VitD-fortified soy beverages for all individuals
aged over 2 years, including pregnant and lactating women
[46]. Two cups of fluid milk will provide 206-210 IU of VitD,
whereas 2 cups of VitD-fortified soy beverages provide 172 IU
VitD [25]. Fluid milk is also fortified (discretionary) to provide
100 IU VitD per cup in the United States [3]. However, because
of this vitamin's limited availability in food sources, reliance
on supplementation is common for individuals to reach the
RDA. Various dosages of VitD in supplements can be found,
ranging from 200 to 1000 IU per tablet [3,25]. VitD
biofortification of foods by adding VitD and/or 25(OH)D to
livestock feeds to increase the VitD/25(OH)D content of the
animal produce or by the use of UV radiation to enhance the
VitD content of foods like mushrooms and baker's yeast is an
emerging means of food-based solutions to tackling VitD
deficiency [53,54].
For pregnant women, the need and effectiveness of taking
a VitD supplement in addition to the diet remain controver-
sial in the literature, and most recommendations target other
nutrients, such as iron and folic acid [55-57]. In 1999, the
United Nations International Children's Emergency Fund,
United Nations University, and World Health Organization
Table 1 – Vitamin D levels, definitions, and recommendations according to different worldwide organizations
Organizations Countries following Vitamin D levels and specifications a Categories DRIs (UL)
these thresholds (nmol/L)

Institutes of Medicine [46,143] United States, Canada Risk of deficiency: <30 Infants 0-6 mo 400 IU b (1000 IU)
Insufficiency: 30-50 Infants 6-12 mo 400 IU b (1500 IU)
Sufficient: ≥50 Pregnant and lactating women 600 IU b (4000 IU)
United Kingdom National United Kingdom Risk of deficiency: <30 Infants 0-6 mo Unspecified
Osteoporosis Society [144] Insufficiency: 30-50 Infants 6-12 mo Unspecified

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Adequacy: ≥50 Pregnant and lactating women Unspecified
Endocrine Society [145] Poland, Hungary, Belarus, Deficiency: <50 Infants 0-6 mo Supplementation 400 IU/d (1000 IU)
Estonia, Czech Republic, Insufficiency: 50-75 Infants 6-12 mo 400-600 IU/d (1000 IU)
Ukraine Adequacy: 75-125 Pregnant and lactating women Supplementation 1500-2000 IU/d (4000 IU)
German Nutrition Society [146] German, Austria, Switzerland Optimal: ≥50 Infants 0-6 mo 800 IU/d
Infants 6-12 mo 800 IU/d
Pregnant and lactating women 800 IU/d
Nordic Nutrition Recommendations Denmark, Finland, Iceland, Insufficiency: <50 Infants 0-6 mo 400 IU/d
2012 [147] Sweden, Norway, the Faroe Adequacy: 50 Infants 6-12 mo 400 IU/d
Island, Greenland, Aaland Pregnant and lactating women 400 IU/d (4000 IU)
Health Council of the The Netherlands Adequacy for people aged between 4 and 70 y: ≥30 Infants 0-6 mo 400 IU/d b
Netherlands [148] Adequacy for people aged 70 y and over: ≥50 Infants 6-12 mo 400 IU/d b
Pregnant and lactating women 400 IU/d b
Australian and New Zealand Australia, New Zealand Mild deficiency: 25-50 Infants 0-6 mo Unspecified
Bone Mineral Society, Endocrine Moderate deficiency: 12.5-25 Infants 6-12 mo Unspecified
Society of Australia, and Severe deficiency: <12.5 Pregnant and lactating women Unspecified
Osteoporosis Australia [149,150]
Canadian Paediatric Society [18] Canada For pregnant/lactating women and infants Infants 0-6 mo 400-800 c IU/d (1000 IU/d)
Deficiency: <25 Infants 6-12 mo 400-800 c IU/d (1500 IU/d)
Insufficiency: 25-75 Pregnant and lactating women 600 IU/d (4000 IU/d)
Adequacy: 75-225

D: day; IU: international units; mo: months; UL: Tolerable Upper Intake Level.
a
For concentrations of serum 25(OH)D.
b
Adequate intakes.
c
Infants living in northern communities (north of 55° latitude) or with dark skin should get 800 IU/d between October and April.

5

Table 2 – Studies on maternal and neonatal risk factors for low neonatal vitamin D stores
Risk factors Authors, year Sample size and study location
Maternal Dror et al, 2012 [151] 80 mother-newborn pairs
vitamin D (40 African Americans and
status 40 non–African Americans)
from Oakland, CA
Dror et al, 2011 [42] 210 mother-newborn pairs
from Oakland, CA
Nicolaidou 123 Healthy mother-newborn
et al, 2006 [90] pairs from Greece
Sachan et al, 2005 [89] 207 urban and rural pregnant
women from Lucknow,
Northern India
Bassir et al, 2001 [88] 50 mother-neonate pairs
from Tehran, Iran
Lee et al, 2007 [40] 40 healthy, mostly black
(62.5%), mother-neonate
pairs from Boston, MA
Bodnar et al, 2007 [16] 400 mother-neonate pairs
from Pittsburgh, PA
Wang et al, 2016 [152] 102 mother-neonate
pairs from China
Intervention or assessment
Maternal venous blood collected at birth
admission and cord blood collected immediately
postdelivery for serum 25(OH)D assays.
Maternal venous blood collected at birth
admission and cord blood collected immediately
postdelivery for serum 25(OH)D assays.
Mothers and cord blood measurement at
delivery: serum 25(OH)D, calcium, phosphorus,
alkaline phosphatase (ALP), PTH,
osteocalcin, and calcitonin
Mothers' measurements at delivery:
serum calcium, inorganic phosphorus, 25(OH)D,
alkaline phosphatase, and PTH.
Cord blood measurements:
alkaline phosphatase and 25(OH)D.
Mothers' measurements at delivery:
serum calcium, 25-OHD, PTH and
phosphatase alkaline.
Cord blood measurements: serum
calcium, 25(OH)D and phosphatase
alkaline levels.
Venous blood was drawn from the
mother and the infant to assess plasma 25(OH)D
concentration 24 to 48 h after birth.
Mothers and cord blood measurements:
Serum 25(OH)D at 4-21 wk of gestation,
at delivery, and in cord blood (n = 200
white and 200 black pregnant women)
Mothers and cord blood measurements at
delivery: serum 25(OH)D.
6
Outcomes
Maternal 25(OH)D concentrations was lower than
umbilical cord concentrations (40.9 nmol/L vs
50.9 nmol/L, P < .001)
African American mothers have lower 25(OH)D
Maternal serum 25(OH)D was positively correlated
with cord blood 25(OH)D (r = 0.79, P < .0001).
Maternal 25(OH)D levels of 41.0 nmol/L vs umbilical
blood concentrations of 51.0 nmol/L (P < .001).
Positive correlation was observed between maternal
and infant 25(OH)D concentrations (r = 0.626, P < .001).
Mean maternal serum 25(OH)D was 35.0 ± 23.3 nmol/L,
and cord blood 25(OH)D was 21.0 ± 14.3 nmol/L. PTH
rose above the normal range when 25(OH)D
N U TR IT ION RE S EA R CH 63 ( 20 1 9 ) 1 – 2 0
was <56.3 nmol/L.
Maternal serum 25(OH)D correlated positively
with cord blood 25(OH)D (r = 0.79, P < .001) and
negatively with PTH (r = 0.35, P < .001).
80% of the women had 25 (OH)D
concentrations <25 nmol/L.
The mean cord serum 25(OH)D concentration was
very low (4.94 ± 9.4 nmol/l) and that of infants of
mother with hypovitaminosis D was almost
undetectable (1.2 ± 1.2 nmol/L).
Of the mothers, 50% (n = 20) were vitamin D deficient,
and most infants were vitamin D deficient (65%; n = 26).
The mean 25(OH)D for black mothers and
infants = 41.1 ± 34.3 nmol/L and 26.6 ± 25.4 nmol/L,
respectively. The 25(OH)D for white mothers and
infants = 51.3 ± 47.6 nmol/L and 38.5 ± 35.2 nmol/L,
respectively.
Overall correlation r2 = 0.68, P < .001 between 25(OH)D
levels in infants and mothers.
At delivery, vitamin D deficiency and insufficiency
occurred in 29.2% and 54.1% of black women and 45.6%
and 46.8% black neonates, respectively.
Five percent and 42.1% of white women and
9.7% and 56.4% of white neonates were
vitamin D deficient and insufficient, respectively.
Prevalence of vitamin D insufficiency was 38.2%
and 26.5% for mothers and neonates, respectively,
whereas 24.5% mothers and 64.7% neonates were
vitamin D deficient.
Neonatal serum 25(OH)D level differed
significantly between the groups of mothers
with different serum 25(OH)D levels (P < .001).
 Risk factors Authors, year Sample size and study location Intervention or assessment

Overall correlations r = 0.914, P < .001 between

Covered Cuhaci-Cakir and 83 Mother-infants
clothing Demirel, 2014 [99], (3-4 mo old) from Ankara, Turkey
Dijkstra 87 neonates of healthy
et al, 2007 [100] mothers with either dark skin
and/or concealing clothing
(risk group) or light skin
(control group) from Rotterdam,
Netherlands.
Mothers and infants measurements: serum
25(OH)D. calcium, inorganic phosphorus,
and alkaline phosphatase.
All infants were receiving 3 drops (400 IU)
of vitamin D3 daily.
Mothers and cord blood measurements:
serum 25(OH)D, alkaline phosphatase, PTH,
ionized calcium and phosphorus.
25(OH)D levels in infants and mothers.
In summer, the rate of vitamin D deficiency was
higher in mothers who wore clothing that
covered nearly all of the body (55%) than in
mothers whose clothing covered less of the
body (13.6%) (P = .016).
In all groups of infants, regardless of seasonal
variation or mothers' clothing style, serum
25-OHD levels and serum concentrations of
Ca, P, and ALP were not statistically different.
A higher prevalence of vitamin D deficiency
was found in the newborn infants of mothers
at risk (63.3%) compared with the control
group (15.8%). Within the risk group, the
neonates of mothers wearing veils were
identified to be at highest risk of vitamin D

N U TR IT ION RE S EA R CH 6 3 ( 20 1 9 ) 1– 2 0
deficiency with a prevalence of 90.9%.
25(OH)D values in pregnant women and
their newborn infants showed a positive
correlation (r = 0.88).
Vitamin D Hollis 350 pregnant women followed RCT, double-blinded, with 3 arms: One month prior delivery, mean 25(OH)D
supplementation/ et al, 2011 [69] from 12-16 wk of gestation (1) daily 400 IU of vitamin D (n = 111), concentration was 118 ± 34.9 nmol/L
RCTs until term from South (2) daily 2000 IU of vitamin D (n = 122), among the 4000 IU group vs 105.4 ± 35.7 nmol/L
Carolina, USA or (3) daily 4000 IU of vitamin D (n = 117). and 79.4 ± 34.3 nmol/L among the 2000 IU
Plasma 25(OH)D was measured at 2 time and the 400 IU groups, respectively (P < .0001).
points: (1) 1 mo prior delivery and (2) at delivery. Similar results were found at delivery: 111.0 ±
40.4 nmol/L for the 4000 IU vs
98.3 ± 34.2 nmol/L in the 2000 IU and
78.9 ± 36.5 nmol/L for the 400 IU dose
group (P < .0001)
82% women achieved 25(OH)D levels
≥80 nmol/L at delivery among the
4000 IU dose group compared to
70.8% in the 2000 IU dose groups
and 50% in the 400 IU (P < .0001).
Cord 25(OH)D was 66.3 ± 25.8 nmol/L
for the 4000 IU group vs 57.0 ± 24.5 nmol/L
in the 2000 IU and 45.5 ± 25.3 nmol/L
in the 400 IU group (P < .0001).
Abrams 49 neonates (27 Hispanic, Serum 25(OH)D and PTH were measured At baseline, mean serum cord 25(OH)D was 55.8 ±
et al, 2012 [73] 22 whites) at birth (cord) and at 3 mo of age. 23.5 nmol/L for white neonates and 41.0 ±
followed up from birth till All infants were on 400 IU/d of 16.3 nmol/L for Hispanic neonates (P = .03).
3 mo of age vitamin D supplements 38 infants returned for 3-mo follow-up (18
from Houston, TX whites and 18 Hispanic). Serum 25(OH)D
increased to 94.5 ± 19.0 nmol/L for white
infants and 78.0 ± 20.3 nmol/L for Hispanic
infants at 3 mo of age (P = .01).

(continued on next page)

7

Table 2
(continued)
Table 2 (continued)
Risk factors Authors, year Sample size and study location
Wagner 257 pregnant women followed
et al, 2013 [74] from 12 to 16 wk of gestation
until term from South
Carolina, USA
Grant 260 pregnant women followed
et al, 2014 [70], from 27 wk of gestation until
term and their infant, from
birth to age 6 mo from
Auckland, New Zealand
Hossain 200 pregnant women followed
et al, 2014 from 20 wk of gestation until
child birth rom Karachi, Pakistan
Perumal 160 pregnant Bangladeshi
et al, 2015 [71], women followed from 26 to
29 wk of gestation until term
from Dhaka, Bangladesh
Sablok 180 pregnant women followed
et al, 2015 [72] from 14 to 20 wk of gestation
until delivery from Delhi, India
Intervention or assessment
RCT, double-blinded with 2000 IU/d (n = 130)
vs 4000 IU/d (n = 127).
Maternal serum total calcium, creatinine, and
inorganic phosphorus were measured bimonthly
also from cord blood at delivery. Intact
PTH was also measured.
RCT, double-blinded, with 3 mother/infant arms:
(1) daily 1000/400 IU of vitamin D (n = 87),
(2) daily 2000/800 IU of vitamin D (n = 86) or
(3) placebo/placebo (n = 87).
Plasma 25(OH)D was measured at 4 time points:
(1) at enrolment; (2) at 36 wk of gestation; (3) in
cord plasma at delivery; and (4) in infants
at 2, 4, and 6 mo of age.
Open-label RCT allocated to 2 groups:
(A) routine care of 200 mg ferrous
sulfate and 600 mg calcium
daily (n = 100) and (B) vitD supplementation
of 4000 IU/d + routine care of
200 mg ferrous sulfate
and 600 mg calcium daily (n = 100).
Maternal serum 25(OH)D was collected
at baseline and delivery. Neonatal vitD
status was assessed
from cord blood at birth or from
neonatal serum samples ≤48 h of birth.
RCT, double-blinded, with 2 arms:
(1) weekly dose of 35 000 IU of
vitamin D (n = 60) or (2) placebo (n = 55).
Plasma 25(OH)D was measured at
3 time points: (1) at delivery including
cord blood, (2) 8 wk
postpartum and, (3) 16 wk postpartum.
RCT, double-blinded, with 4 arms:
(1) a total of 60 000 IU of vitamin D
(n = 28), (2) 240 000 IU
of vitamin D (n = 27), (3) 480000 IU
of vitamin D (n = 53), and
8
Outcomes
Overall maternal 25(OH)D change from
baseline was +14.1 ng/mL (SD12.7 P < .001).
No statistically significant difference
between the 2000-IU and the 4000-IU
groups at last visit prior to delivery.
Mean cord blood 25(OH)D was 27.0 ±
13.3 ng/mL among the 4000-IU group
vs 22.1 ± 10.3 ng/mL in the 2000-IU group (P = .024).
Significant differences between placebo
group and the lower-dose or the
higher-dose group during gestation
(both P < .001) and in cord blood
(P = .002 vs P < .001).
N U TR IT ION RE S EA R CH 63 ( 20 1 9 ) 1 – 2 0
No significant differences observed
between the intervention groups.
For infants, significant differences
between placebo and the lower-dose
or the higher-dose group were also
reported for infants at 2 mo (both
P < .001) and at 4 mo (P = .02 vs P < .001).
At birth, maternal 25(OH)D was increased in
group B (18.3 ± 11 ng/dL vs 8.82 ± 11.84 ng/dL,
P = 0 .001) compared with group A (6.9 ±
7.0 ng/dL vs 6.32 ± 3.97 ng/dL, P = .06).
Neonatal 25OHD levels were significantly
higher in group B compared with group A
(19.22 ± 12.19 ng/dL vs 6.27 ± 5.2 ng/dL).
Maternal and neonatal 25OHD concentrations
were positively correlated (r = 0.83, P = .001).
Mean 25(OH)D at delivery was 134 ± 31 nmol/L for
the supplemented group vs 37 ± 18 nmol/L for the
placebo group (P < .001).
Mean 25(OH)D at 8 wk postpartum for the
supplemented group was 62 ± 15 vs 38 ±
16 nmol/L for the placebo group (P < .001).
The effect was attenuated at 16 wk after delivery
(55 ± 16 vs 47 ± 17 nmol/L; P = .06), respectively.
All treated mothers showed an increase in 25(OH)D
levels after supplementation, with median levels of
65 nmol/L postsupplementation compared to
35 nmol/L presupplementation and 24 nmol/L
in the nonintervention group. Significance not reported.
 Risk factors Authors, year Sample size and study location Intervention or assessment

(4) nonintervention (n = 60). Fewer infants from nonintervention group

Plasma 25(OH)D was measured at had serum 25(OH)D greater than 50 nmol/L
2 time points: (1) at enrolment and (2) compared to infants in the intervention
at delivery including cord blood. groups (14% vs 46.2%; P < .001).
Prepregnancy Bodnar 400 mother-neonate pairs Mothers and cord blood measurements: Compared with women with BMI <25, pregravid
and pregnancy et al, 2007 [41] from Pittsburgh, PA serum 25(OH)D at 4-21 wk of obese women with BMI ≥ 30 had lower adjusted
BMI gestation, predelivery, and at delivery. mean serum 25(OH)D concentrations at 4-22 wk
(56.5 vs. 62.7 nmol/L; P < .05) and a higher
prevalence of vitamin D deficiency (61 vs. 36%; P < .01).
Vitamin D concentration of neonates born to
obese mothers was lower than neonates of
lean mothers (adjusted mean, 50.1 vs.
56.3 nmol/L; P < .05).
An increase in BMI from 22 to 34 was associated
with 2-fold (95% CI, 1.2-3.6) and 2.1-fold (1.2-3.8)
increases in the odds of midpregnancy and
neonatal vitamin D deficiency, respectively.
Women with prepregnancy BMI ≥35 kg/m2 had

Woolcott 1635 pregnant women from
et al, 2016 [14] Quebec City and Halifax, Canada
Josefson 360 white mother-neonate pairs
et al, 2016 [112] from Chicago, IL; Cleveland, OH;
and Toronto, Ontario, Canada
Smoking/ Diaz-Gomez 61 mother-neonate pairs
cigarette smoke et al, 2007 [139], (n = 32 smoking women vs
exposure n = 29 nonsmoking women)
from Canary Island, Spain
Banihosseini 108 mother-neonate pair
et al, 2013 [153], (n = 54 exposed to cigarette
smoke vs n = 54 nonexposed
women) from Tehran, Iran.
Gangat 68 newborns from
et al, 2012 [96], New Orleans, LA
Serum maternal blood assessed for
25(OH)D at 15 wk of gestation and
neonatal cord blood at delivery
Serum maternal and cord blood
were assessed for 25(OH)D
25(OH)D, 1,25 (OH)2D, calcium,
phosphorus, and alkaline
phosphatase were assessed
from blood samples of mothers
during the last trimester of
pregnancy. Infants were
assessed at 2 to 3 d old.
Mothers and cord blood
measurement at delivery: 25(OH)D, PTH,
calcium, and alkaline phosphatase.
25(OH)D levels were measured from
blood samples collected
from cord blood, at 2 and 4 mo of age
N U TR IT ION RE S EA R CH 6 3 ( 20 1 9 ) 1– 2 0
8.2 nmol/L (4.0-12.3) serum 25(OH)D less than
women with prepregnancy BMI <25 kg/m2
Cord blood 25(OH)D was lower by 6.1 nmol/L
(0.5-12.8) with maternal BMI 30-<35 compared
to BMI <25 kg/m2
Maternal serum 25(OH)D was lower by
0.40 ng/ml for BMI higher by 1 kg/m2
(P < .001) after adjusting for other covariates.
Cord blood 25-OHD was lower by 0.26 ng/ml for
maternal BMI higher by 1 kg/m2 (P < .004).
Newborns of mothers who smoked had significantly l
ower serum 25(OH)D (14.2 ± 6.2 ng/mL vs 22.3 ±
11.3 ng/mL, P = .009).
No significant difference in the mean 25(OH)D
in maternal serum in exposed and nonexposed group.
No significant difference in the mean
concentration of 25(OH)D in cord serum of
exposed and nonexposed group.
Significant correlation between maternal
and umbilical cord serum 25(OH)D in both
exposed and nonexposed subjects
(r = 0.824, P < .001).
African American infants had lower 25(OH)D
levels compared with white infants (43 ±
2.8 nmol/L vs 69.2 ± 4.2 nmol/L, P < .001)
respectively, at birth.
No significant correlation was seen between

9
(continued on next page)

Table 2
(continued)
Table 2 (continued)
Risk factors Authors, year Sample size and study location
Skin Dror 80 mother-newborn pair
pigmentation/ et al, 2012 [151] (40 African Americans
ethnicity and 40 non–African
Americans) from Oakland, CA
Dror et al, 2011 [42] 210 mother-newborn pair
(107 African Americans and
93 non–African Americans)
from Oakland, CA
Abrams 49 neonates (27 Hispanic,
et al, 2012 [73], 22 whites) followed up from
birth till 3 mo of age from
Houston, TX
Seasonal Gangat 68 newborns from
variation et al, 2012 [96] New Orleans, LA
Dror et al, 2011 [42] 210 mother-newborn pair
(107 African Americans
and 93 non–African
Americans) from Oakland, CA
Dijkstra 87 neonates of healthy
et al, 2007 [100] mothers with either dark
skin and/or concealing
clothing (risk group) or
light skin (control group)
from Rotterdam, Netherlands.
Cuhaci-Cakir and F 83 Mother-infants (3-4 mo old)
Demirel, 2014 [99], from Ankara, Turkey
Intervention or assessment
Maternal venous blood collected at labor
admission and cord blood collected
immediately postdelivery for
serum 25(OH)D assays.
Maternal venous blood collected at
labor admission and cord
blood collected immediately
postdelivery for serum 25(OH)D assays.
Serum 25(OH)D and PTH were
measured at birth (cord)
and at 3 mo of age.
All infants were on 400 IU/d
of vitamin D supplements
25(OH)D levels were measured
from blood samples collected from
cord blood, at 2 and 4 mo of age
Maternal venous blood collected
at labor admission and cord blood
collected immediately postdelivery
for serum 25(OH)D assays.
Mothers and cord blood measurements
at delivery: serum 25(OH)D, alkaline
phosphatase, PTH, ionized calcium,
and phosphorus.
Serum 25(OH)D. calcium, inorganic
phosphorus, and alkaline phosphatase
were measured from both mothers
and infants blood samples.
10
Outcomes
25(OH)D cord blood values and levels at
2 mo and 4 mo.
African American mothers have lower
25(OH)D compared to non–African American
mothers (69.1 ± 26.1 vs 82.3 ± 30.3 nmol/L, P = .04).
Also, African American neonates have lower
cord 25(OH)D compared to non–African
American neonates (36.0 vs 48.2 nmol/L P = .004)
African American mothers have lower
25(OH)D compared to non–African American
mothers (69.2 ± 32.4 vs 78.7 ± 34.5 nmol/L, P = .046).
Also, African American neonates have
lower cord 25(OH)D compared to non–African
N U TR IT ION RE S EA R CH 63 ( 20 1 9 ) 1 – 2 0
American neonates (39.1 ± 20.5 vs 48.7 ±
24.7 nmol/L P = .001)
At baseline, mean serum cord 25(OH)D was
lower for Hispanic neonates compared to white
neonates (41.0 ± 16.3 vs 55.8 ± 23.5 nmol/L, P = .03).
Also at 3-mo follow-up (38 infants returned
for 3-mo follow-up; 18 whites and 18 Hispanic),
serum 25(OH)D remained lower for Hispanic
infants compared to white infants (78.0 ±
20.3 nmol/L vs 94.5 ± 19.0 nmol/L; P = .01).
Mean 25(OH)D levels were lower in the winter
(44.1 ± 4.9 nmol/L, n = 12) and summer
(52.2 ± 3.6 nmol/L, n = 24) and higher in the
spring (61.0 ± 9.7 nmol/L, n = 12) and fall
(72.0 ± 6.1 nmol/L, n = 20), P < .05).
Prevalence of serum 25(OH)D < 75 nmol/L was
highest in African American mothers who
delivered in late winter/early spring (78.6%)
and lowest in non–African American
mothers who delivered in late
summer/early fall (36.4%).
The mean serum 25(OH)D values did not
differ significantly between the seasons
of birth in both groups.
In summer, the rate of vitamin D deficiency was
higher in mothers who wore clothing that
covered nearly all of the body (55%) than in
mothers whose clothing covered less of the
body (13.6%) (P = .016).
 N U TR IT ION RE S EA R CH 6 3 ( 20 1 9 ) 1– 2 0 11

released a proposition about the composition of a multinutrient

supplement providing the daily recommended allowance of
vitamins, including 200 IU of VitD for pregnant women [58].
differences based on their clothing style (P > .05).

of Ca, P, and ALP were not statistically different.

serum 25-OHD levels and serum concentrations
seasonal variation or mothers' clothing style, Today, several organizations, including Health Canada and the
insufficiency, and there were no significant

American Dietetic Association, encourage women to take a

In the winter, nearly half of both groups of

prenatal multivitamin daily during their pregnancy [18,55,59-

mothers had vitamin D deficiency or

In all groups of infants, regardless of

61]. Most prenatal multivitamins contain 400 IU of VitD, although

a panel of experts specifically suggests a daily dose of 600 IU
Intervention or assessment

supplemental VitD for women during pregnancy to prevent

nutritional rickets in infants [62]. To maintain maternal 25(OH)D
concentrations in the targeted range, intake exceeding 600 IU/d
may be needed [1,18,63].
D: day; CA: California; IL: Illinois; IU: international units; LA: Louisiana; MA: Massachusetts; Mo: months; OH: Ohio; PA: Pennsylvania; TX: Texas; Wk: weeks.

4.2. Dietary intake and use of supplements

4.2.1. Dietary intake

In North America, fortified dairy and dietary supplements are
the main dietary source of VitD [3,64]. The Maternal-Infant
Research on Environmental Chemicals (MIREC) study across
Canada identified milk (52.3%), fish (all species) (9.1%), and
yogurt (8.6%) as the 3 major food components that contrib-
uted to dietary VitD intakes [65]. Aghajafari et al [66] observed
a significant increase of 168 IU in VitD intake from diet and
Sample size and study location

All infants were receiving 3 drops

supplements from the first to the third trimester among

pregnant women in Alberta. However, 44% of the pregnant
(400 IU) of vitamin D3 daily.

women did not meet the VitD DRI of 600 IU/d because of
limited VitD from food and beverages [66]. Furthermore, the
US National Health and Nutrition Examination Survey
(NHANES) data showed that 66% of the pregnant women
studied did not take VitD supplements, whereas 19% took
supplements containing <400 IU/d [67]. The authors con-
cluded that current US VitD supplementation recommenda-
tions of 400 IU/d might not be adequate for many pregnant
women and their infants [67].

4.2.2. Use of supplements

4.2.2.1. Vitamin D supplementation. Routine supplementa-

tion of pregnant women has been considered as a strategy to
increase newborn stores of VitD. Several questions remain
Authors, year

about the optimal period to take supplemental VitD and how

much maternal supplementation is enough to support
maternal and fetal stores. Few studies have focused specifi-
cally on VitD during pregnancy. A subsample of pregnant
women (n = 1186) from the MIREC study reported that VitD
supplemental intake accounted for a median of 60% of total
VitD intake [65]. A study carried out in Oakland, CA, showed
significant correlations between average maternal VitD intake
(food and supplement) with maternal and cord serum 25(OH)
Risk factors

D (r = 0.26 and r = 0.33, P < .001, respectively) [42]. Overall,

there is good support for maternal supplementation as a
strategy to support neonatal 25(OH)D concentrations [68].
Table 2 summarizes the main outcomes of VitD intervention
studies on pregnant women and neonates [69-75]. A meta-
analysis [68] on supplemental VitD during pregnancy showed a
mean difference of 54.7 nmol/L of serum 25(OH)D concentration
among participants who received a supplement compared to
placebo/control groups. Daily supplementation allowed women
to reach higher 25(OH)D concentrations at term compared to a
single oral dose of VitD. On the other hand, the main responses
12 N U TR IT ION RE S EA R CH 63 ( 20 1 9 ) 1 – 2 0
were highly heterogeneous, which could be explained by
different doses, inception points, and methods to assess serum
25(OH)D used in the analyzed trials [68]. The effect of maternal
VitD supplementation on neonates has also been shown through
randomized controlled trials [69,70,72]. Gangat et al reported that
neonates whose mothers received placebo during pregnancy had
significantly lower cord blood 25(OH)D compared to those whose
mothers received 400 and 800 IU/d (32.5 vs 60.0 and 65.0 nmol/L;
P < .001, respectively) [70]. Similarly, Hollis et al reported that
cord 25(OH)D was 45.5 ± 25.3 nmol/L for neonates born to
mothers who received 400 IU/d vs 57.0 ± 24.5 nmol/L in the
2000-IU/d and 66.3 ± 25.8 nmol/L in the 4000-IU/d groups
(P < .0001) [69]. Overall, in a recent meta-analysis, maternal VitD
supplement use was associated with a mean difference of
34 nmol/L (95% CI, 25-42) in cord blood [76].
There is a general consensus for breast-fed infants to be
supplemented with 400 IU VitD/d because of low VitD content
of human milk [1,17,46]. Despite the recommendation, the
NHANES study reported an 8.7% (SE 1.3%) prevalence of VitD
supplement use in US infants aged 0-11 months [77], whereas
a review on hypovitaminosis D in the United States reported
that the most (78%) severely VitD-deficient infants were those
breast-fed in winter who did not receive VitD supplementa-
tion [47]. Formula-fed infants were not included in the
recommended daily supplementation of 400 IU because
infant formulas provide 400 IU of VitD/L [46,78]. However, to
reach the requirements, formula-fed infants need to consume
1 L/d [79], which is not typical [80].
4.2.2.2. Adherence to supplementation. Adherence to sup-
plementation is another factor that can impact both maternal
and infant VitD stores. The 2015 Canadian Community Health
Survey reported that only 42.7% (Coefficient of variation, 2.7%) of
women ≥19 years used VitD supplements [81]. Sociodemographic
factors including racial disparities contribute to differences in
adherence to supplementation. For instance, black women
were found to adhere significantly less to prenatal supplemen-
tation compared to white women (72% vs 79%; P ≤ .01) [82].
Similarly, a US national cohort study reported that women
of ethnic minority and lower economic status were more
likely not to use a daily VitD supplement (OR [95% CI] of
2.7 [2.1-3.6] and 2.8 [2.3-3.5] for non-Hispanic blacks and
Hispanics, respectively), which could influence the concentra-
tions of serum 25(OH)D [67].
There were also differences in use of VitD supplements in
infancy based on race/ethnicity in Canada [83]. A lower
percentage of black mothers (57.5%) reportedly provided
their breast-fed infants with VitD supplements compared to
73.7% of Asian and 75.9% of white mothers [83]. The NHANES
study equally reported significant differences in VitD supple-
ment use among children from age 0 to 18 years based on
race/ethnicity [77], with 15.5% of non-Hispanic blacks using
VitD a supplement compared to 18.6% and 31.0% of Mexican
Americans and non-Hispanic whites, respectively [77].
There are other barriers and facilitators of adherence to
supplementation. For example, women's beliefs about sever-
ity of nutrient deficiencies, low perceptions of susceptibility
to develop deficiencies, and limited knowledge about micro-
nutrient deficiencies other than iron were reported barriers to
initiation of supplement use among prepregnant, pregnant,
and postpartum women [84]. Conversely, perceived health
benefits [85], a recommendation by a health care professional,
and blood test results [85] were reported to enhance adher-
ence to supplement use. The brand, dosage, cost, and safety
of supplements were also factors considered when buying a
supplement [85]. Based on the recommendation for taking
VitD by a health professional being a facilitator, Awker et al
[86] thus looked at the impact of a clinic-wide VitD protocol on
pregnant women and reported that women were more likely
to take VitD supplements when it was prescribed.
4.2.3. Population statistics on vitamin D supplementation of
infants
Despite the international recommendation to provide a daily
VitD supplement to breast-fed infants, putting it into practice
seems to be a challenge. A survey of 16 389 US infants aged 1-
10.5 months showed that <8% of the infants received oral
VitD supplementation [80]. One-month-old infants had the
lowest VitD supplementation prevalence (3.9%), with the
highest prevalence among the 5-month-old infants (7.3%)
[80]. Furthermore, the 2009-2012 NHANES study suggested
that less than 1 in 5 breast-fed infants met the VitD
recommendation of 400 IU/d compared to nearly 1 in 3 non–
breast-fed infants [78].
According to the results of the 2009-2010 Canadian
Community Health Survey, 74.1% of breast-fed infants re-
ceived the recommended intake of VitD on a given day [83].
The percentages of individuals who gave VitD containing
supplements were lower among mothers with lower income
(67.3% from the lowest quintile vs 83.0% from the highest
quintile) and education (less than secondary graduation,
63.7% vs postsecondary graduation, 77.5%). As previously
discussed, ethnic background was also highlighted in this
survey [83]. Years since immigration was also important,
where 66.4% of recent immigrants of <5 years gave their
infant a VitD supplement compared to 75.6% of those who
immigrated ≥5 years ago [83]. More married or common-law
mothers gave a VitD supplement to their breast-fed infants
compared to single, divorced, separated, or widowed mothers
(75.4% vs 65.8%). On a regional level in Canada, the province of
Ontario had a significantly lower percentage of breast-fed
infants on VitD supplementation (68.9%) than the national
average (74.1%), whereas the Prairies region had the highest
level (82.8%). In the Quebec region, the percentage was 74.5%
which is close to the Canadian average where about 3 of 4
breast-feeding mothers followed the Health Canada recom-
mendation to provide their infants with a supplement
containing VitD [83].
4.3. Maternal vitamin D status
Low VitD status during pregnancy is a major issue identified
in a number of studies (Table 2). The NHANES data reported
that 33% (95% CI, 28-40) of the pregnant women studied had
25(OH)D < 50 nmol/L and 7% (95% CI, 4-10) had 25(OH)
D < 25 nmol/L [67]. The study also showed that minority
race/ethnicity, lower socioeconomic status (SES), younger age,
pregnancy, and later trimester were independently associated
with lack of VitD supplementation. There is a lack of national
surveys regarding VitD status of pregnant women in Canada.
 N U TR IT ION RE S EA R CH 6 3 ( 20 1 9 ) 1– 2 0
However, a study on 467 pregnant women reported that 31.5%
had 25(OH)D concentrations <50 nmol/L (mean concentra-
tions: 26.3 ± 9.4 nmol/L) [87]. Studies from different countries
equally observed significant and strong correlations between
infant 25(OH)D concentrations and maternal values during
gestation [16,88], at delivery (cord blood) [75,88-90], and 24-
48 hours after birth [40,75] (Table 2).
Maternal VitD deficiency is commonplace in temperate
latitudes and is a major risk factor for low 25(OH)D concen-
trations in infancy [18]. Adequate VitD status during preg-
nancy is known to be important for fetal skeletal
development, general growth, and even tooth enamel devel-
opment [91] and is a preventive measure against adverse
outcomes, but it is not a guarantee that neonates will have
sufficient concentrations at birth [16,90]. A target of 75 nmol/L
serum 25(OH)D for pregnant women as discussed earlier
[49,50] might be more beneficial, as it is well established that
neonatal 25(OH)D is usually lower than maternal concentra-
tions (Table 2). Therefore, the importance of achieving
sufficient VitD status in mothers as a result of intake from
all sources needs consideration.
4.4. Sunlight exposure, ethnicity, and skin pigmentation
Several factors influence the amount of ultraviolet exposure
available for the photosynthesis of VitD, including skin
pigmentation, sunshine exposure, seasonal variation, geo-
graphical location, and ultraviolet protection (clothing, sun-
screen). It was reported in adults (30-39 years) that those with
lighter skin pigmentation who expose their body to sunlight
for 10-15 minutes during summertime will generate between
10 000 and 20 000 IU of VitD, whereas dark-skinned individ-
uals need about 5-10 times more exposure to synthesize the
same amount of VitD [1,92]. The degree of melanin content
affects VitD production by absorbing ultraviolet rays. The
more melanin the skin contains, the less ultraviolet beta rays
are available to activate endogenous VitD production [93].
Thus, individuals with darker skin pigmentation ranging from
dark (skin type IV) to black (skin type VI), such as black or
West Indian individuals, require substantially more sunlight
exposure for the synthesis of VitD.
In the literature, ethnic background seems to be another risk
factor leading to low neonatal VitD status, mostly related to low
maternal serum 25(OH)D concentrations. A study reported lower
VitD values among black women (46.3 ± 21.0 nmol/L) compared
to Hispanics (65.3 ± 18.8 nmol/L) and whites (73.8 ± 36.0 nmol/L;
P < .001) at first trimester [74]. Dror et al also reported signifi-
cantly lower mean serum 25(OH)D in African American women
(69.2 ± 32.4 nmol/L) and infants (39.1 ± 20.5 nmol/L) compared to
non–African American women (78.7 ± 34.5 nmol/L; P = .046) and
infants (48.7 ± 24.7 nmol/L); P < .001); the study however found
skin pigmentation to be a more sensitive index of VitD status
than racial origin [42].
One study tried to genetically explain these VitD race-
related disparities between black and white individuals and
found that levels of VDBP were lower in black people than in
whites (168 ± 3 μg/mL vs 337 ± 5 μg/mL, respectively; P < .001)
[94]. Variation in VDBP levels may in part be responsible for
racial differences in 25(OH)D concentrations [94]. However,
previous findings reported similar VDBP levels among white,
13
black, Indian, and Asian people [92]. Different assays for VDBP
often have different affinities for different VDBP epitopes,
which might make results inconsistent. This reinforces the
need for further research on genetic disparities between
ethnicity for VitD production and concentrations.
In a recent meta-analysis, Martin et al [95] reported a high
prevalence of VitD deficiency in dark-skinned individuals,
including pregnant women. Correlations between cord blood
25(OH)D concentrations and skin pigmentation among black
and white infants showed significantly lower VitD concen-
trations for infants with darker skin pigmentation compared
to the white group (43 ± 2.8 nmol/L vs 69.2 ± 4.2 nmol/L,
respectively; P < .001) [96]. The development of skin colora-
tion begins at the embryo stage and continues after birth.
Prior to 32 weeks of gestation, black and white infants exhibit
a similar pattern of skin pigmentation, but skin color of black
infants becomes darker, whereas white ones retain their light
skin color [97]. The skin of newborns is not fully pigmented
because of the relatively low production of melanin during
the fetal and neonatal periods but will mature during the 6
months following birth [98]. Considering these physiological
changes, assessing skin pigmentation of newborns is likely
not the best practice to determine their risk of low VitD status,
and maternal natural skin coloration should be considered
instead.
4.5. Seasonal variations and clothing
The effect of seasonal variations on maternal VitD status
results in 25(OH)D concentrations being lowest in winter in
North America [87,96]. In a cohort of pregnant women living
in Toronto, Canada, prevalence rates of VitD deficiency were
31.3%, 29.9%, 17.0%, and 21.8% in winter, spring, summer, and
fall seasons, respectively (P = .006) [87]. Gangat et al [96]
equally reported lowest cord blood 25(OH)D concentrations
(nmol/L) in winter (44.1 ± 4.9) compared to summer (52.2 ±
3.6), spring (61.0 ± 9.7), and fall (72.0 ± 6.1) (P < .05) in South-
ern Louisiana, USA.
Clothing is also a factor limiting the exposure of skin to
solar radiation and varies according to the season. Although
there seems to be scarcity of data on effects of clothing style
on maternal VitD status in North America, such studies have
been carried out outside North America [72,99,100]. Cuhaci-
Cakir and Demirel investigated the VitD status of Turkish
mothers and their 3- to 4-month-old infants according to
season and mother's clothing style [99]. In summer, signifi-
cantly lower serum 25(OH)D concentrations were found in
covered mothers (hair, arms, and legs completely covered)
compared to mothers not wearing covered clothing
(34.5 nmol/L vs 58.5 nmol/L, respectively; P < .001). During
the winter season, 25% of mothers in both groups were VitD
deficient [<37.5 nmol/L 25(OH)D], and another 25% were VitD
insufficient (<50 nmol/L). Very low rates of VitD deficiency
were found in all infant groups as assessed at 3-4 months of
age as a result of daily VitD supplementation since birth [99].
However, an earlier study in Rotterdam, Amsterdam, reported
a higher prevalence of VitD deficiency among neonates of
veiled mothers or mothers with dark skin in association with
low (12.5%) use of VitD supplements [100]. The practice of
purdah—the custom of fully covering women with clothing—
14 N U TR IT ION RE S EA R CH 63 ( 20 1 9 ) 1 – 2 0
might be a major contributing factor to VitD deficiency observed
in Iranian pregnant mothers and their neonates [88]. Overall,
wintertime is the major limiting factor in the production of VitD;
however, even during summer months, clothing and avoidance
of the sun can also reduce its production.
4.6. Professional opinion
As reported previously, there are important divergent opinions of
health professionals about VitD supplementation. Previous
studies reported that few pediatric health care providers
recommend VitD for breast-fed infants [101-103] despite the
World Health Organization recommendation to provide a VitD
supplement to children if exposure to sunlight is not possible
[104]. Reasons for these include belief that a recommendation of
supplementation might discourage mothers from breast-feeding
[103], assumption that human milk contains adequate VitD
[101,102,105] and belief that infants were sufficiently exposed to
sunlight [102,105]. Importantly, health care professional opinions
can affect maternal behaviors, possibly leading to low neonatal
25(OH)D concentrations.
4.7. SES and education
SES was another factor reported in the literature that could
influence 25(OH)D concentrations of pregnant women. In
their secondary analysis of the US NHANES 2001-2006, Ginde
et al [67] pointed out different characteristics of nonpregnant
and pregnant women in relation to their VitD status. Higher
serum 25(OH)D concentrations were associated with higher
SES, the use of a VitD supplement, longer duration of the
supplementation, and greater outdoor physical activity. In a
multiethnic Canadian population, despite the high levels of
education and SES of the pregnant women studied, VitD
insufficiency remained common, with 24% of women with
serum 25(OH)D concentrations <50 nmol/L [106]. The MIREC
study reported a higher proportion of women with lower VitD
intake to have less than a university degree with family
income less than CA $60 000, which is below the Canadian
median family income of $86 000 [65,107]. Thus, SES and
educational levels should be considered when educating
mothers, notably because of the low adherence to maternal
and neonatal supplementation reported among populations
with lower SES and education [67,83].
4.8. Maternal morbidities/pregnancy complications
It is estimated that low VitD status accounts for about 10% of
pregnancy complications in Canada [108]. A combined dataset of
2 US randomized clinical trials of VitD supplementation during
pregnancy concluded that maternal delivery 25(OH)D was
inversely associated with pregnancy comorbidities, with fewer
events as 25(OH)D increased [109]. As discussed earlier,
hypovitaminosis D has been associated with a number of health
problems in offspring and potentially with maternal morbidities.
4.8.1. Body mass index
Obesity has been reported to be another risk factor for
deficient levels of VitD because of the sequestration of VitD
in adipose tissue [110]. The Framingham Heart Study on more
than 3000 adults reported an inverse association between
VitD and waist circumference, with the prevalence of VitD
deficiency 3-fold higher in adults with high subcutaneous
adipose tissue and visceral adipose tissue compared to those
with low subcutaneous adipose tissue and visceral adipose
tissue (15.8 vs 5.1%, P < .001) [111]. Because VitD deficiency
might mediate adverse pregnancy outcomes related to
prepregnancy BMI, Bodnar et al [41] investigated the relation-
ship between serum 25(OH)D and prepregnancy BMI in a
pregnancy cohort. A negative correlation was found between
prepregnancy BMI and 25(OH)D concentrations at term
(r = −0.19; P < .001) and in cord blood 25(OH)D concentrations
(r = −0.18; P < .0001). An increase in prepregnancy BMI from 22
to 34 kg/m2 was associated with 2.1-fold (95% CI, 1.2-3.8)
increase in the odds of neonatal VitD deficiency [41]. Another
pregnancy cohort reported that women with prepregnancy BMI
≥35 kg/m2 had 8.2 nmol/L (4.0-12.3) serum 25(OH)D less than
women with prepregnancy BMI <25 kg/m2 [14]. Similarly, in a
multicenter study with mother-neonate pairs at 28 weeks’
gestation, higher BMI in pregnancy was associated with
lower maternal 25(OH)D concentrations. However, results
did not show a significant relationship between neonatal
serum 25(OH)D concentrations and maternal BMI [112].
Nevertheless, BMI cutoff should not be used for pregnant
cohorts [113], and this could be an important limitation in
studies examining maternal obesity in pregnancy and serum
25(OH)D concentrations.
Despite the dearth of data about direct relationships
between maternal VitD status and weight gain during
pregnancy, 25(OH)D is inversely associated with adiposity
and VitD deficiency strongly linked with variation in subcu-
taneous and visceral adiposity [111]. However, the possibility
that behaviors related to maternal body weight and maternal
serum 25(OH)D concentrations interact to regulate infant 25
(OH)D concentrations requires further investigation.
4.8.2. Hypertensive disease in pregnancy
Pregnancy-induced hypertension (PIH), also known as preeclamp-
sia and its advanced stage eclampsia, is a pregnancy-specific
syndrome associated with adverse pregnancy outcomes. The
biological cause of preeclampsia involves a number of processes
that may be affected by VitD directly or indirectly; this includes
placental implantation, abnormal angiogenesis, immune dys-
function, excessive inflammation, renin-angiotensin-aldosterone
system, and hypertension [114-117].
Bodnar et al [118] demonstrated that maternal VitD
deficiency in early pregnancy was a strong, independent risk
factor for preeclampsia. The study observed a 5-fold increase
in the odds of preeclampsia using the 1997 IOM definition of
25(OH)D < 37.5 nmol/L [118]. Also, 2 more recent case-
controlled studies demonstrated that maternal VitD defi-
ciency in early pregnancy [119] and midpregnancy [120] is an
independent risk factor for preeclampsia even after adjusting
for multiple covariates [119]. Rostami et al showed a 9%
decrease in preeclampsia risk among pregnant women
supplemented with VitD compared to those who did not
receive supplements [121]. Also, the Vitamin D Antenatal
Asthma Reduction Trial reported a significantly lower risk of
preeclampsia among women with 25(OH)D ≥ 75 nmol/L com-
pared to women with 25(OH)D < 75 nmol/L in both early and
 N U TR IT ION RE S EA R CH 6 3 ( 20 1 9 ) 1– 2 0
late pregnancy (adjusted OR, 0.28; CI, 0.08-0.96; P = .04) [122].
Furthermore, another recent VitD supplementation trial
reported fewer preeclampsia events (1.2% vs 7.4%, P < .05)
and fewer cases of intrauterine growth restriction (9.6% vs
22.2, P = .03) among pregnant women supplemented with
4000 IU/d VitD compared to those supplemented with 400 IU/d
[123]. In another Iranian study, pregnant women with previous
history of preeclampsia and baseline 25(OH)D ≥ 25 ng/ml
(n = 142) were randomized into intervention (50 000 IU cho-
lecalciferol once every 2 weeks; n = 70) and control (placebo;
n = 72) groups [124]. The study reported a 1.94 (95% CI, 1.02-
3.71) higher risk of preeclampsia for control group compared
to the intervention group (P = .036) [124]. Wei et al reported
that pregnant women with 25(OH)D < 50 nmol/L have an in-
creased risk of developing preeclampsia (OR, 2.09 [1.50-2.90])
[125]. Higher odds (OR, 1.79 [1.25-2.58]) of developing pre-
eclampsia when 25(OH)D concentration is <75 nmol/L were
also reported in another meta-analysis [31]. To the best of our
knowledge, no study has reported on the associations
between PIH and neonatal 25(OH)D concentrations at birth.
Furthermore, recommendations for the prevention of pre-
eclampsia do not specifically include a targeted intake of
VitD to threshold of VitD status at this time [126].
4.8.3. Gestational diabetes mellitus
Gestational diabetes mellitus (GDM) is a temporary condition of
pregnancy which has been associated with a high risk of future
type 2 diabetes mellitus [127]. A potential mechanism to explain
the relationship between VitD insufficiency and the risk of
GDM includes the direct effect of VitD on β-cell function, as low
serum 25(OH)D decreases β-cell function and insulin sensitivity
[128]. Studies have shown inconsistent associations between
maternal VitD status and glycemia [129-131] with a shortage of
evidence from high-latitude regions like Canada or the northern
states of the USA [87]. However, 2 studies reported associations
between VitD insufficiency in early pregnancy and increased risk
of developing GDM over the course of pregnancy [132,133].
Furthermore, another study reported inverse associations be-
tween VitD status and GDM among women who smoke during
pregnancy [134].
A trial in 120 pregnant women from Yazd, Iran, reported a
decrease in insulin resistance among women supplemented
with 50 000 IU VitD every 2 weeks compared to pregnant women
on 200 IU/d (Homeostatic model assessment of insulin resistance
(HOMA-IR); 0.7 ± 1.04 vs 1.46 ± 1.69, P = .02) [135]. Another trial in
60 women with GDM in Iran reported better maternal and
neonatal outcomes in women supplemented with 1000 mg
calcium per day plus 2 doses of 50 000 IU cholecalciferol (1 at
baseline and another at day 21 of the trial) compared to women in
the placebo group [136]. Specifically, there were lower cesarean
sections (23·3% vs 63·3%, P = 0·002), maternal hospitalizations (0
vs 13·3%, P = 0·03), macrosomia (0 vs 13·3%, P = 0·03),
hyperbilirubinemia (20·0% vs 56·7%, P = 0·03), and neonatal
hospitalizations (20·0% vs 56·7%, P = 0·03) in the supplemented
compared to placebo group [136].
A meta-analysis reported that pregnant women with 25
(OH)D < 50 nmol/L have an increased risk of developing GDM
(OR 1.38 [1.12-1.70]) [125], whereas another reported slightly
higher odds of GDM when 25(OH)D concentration is <75 nmol/L
(OR 1.49 [1.18-1.89]) [31].
15
A cohort study on 184 pregnant women with GDM reported
that neonates born to mothers with 25(OH)D < 50 nmol/L had
more adverse outcomes compared to neonates born to
mothers with 25(OH)D > 50 nmol/L [137]. Specifically, neo-
nates born to mothers with 25(OH)D < 50 nmol/L were more
frequently small-for-gestational-age (17.3% vs 5.9%, P = .017),
had higher incidences of hospitalization in intensive care
units (32% vs 19%, P = .048), and had higher incidence of
hypoglycemia (17.3% vs 7.1%, P = .039) compared to their
counterparts [137]. Also Asemi et al reported a lower
incidence of hyperbilirubinemia among neonates born to
mothers supplemented with VitD compared to the placebo
group (27.3% vs 60.9% P = .02) [138]. To date, there is not
enough conclusive evidence to incorporate into specific
recommendations of VitD supplementation for pregnant
women with GDM to support optimal maternal and neonatal
outcomes. However, it is important to ensure that maternal
25(OH)D concentrations are at least sufficient, especially in
the presence of pregnancy complications with potential to
negatively impact maternal-fetal transfer.
4.9. Lifestyle factors
4.9.1. Smoking status
The mechanism by which smoking could be associated with
decreased circulating concentrations of VitD, especially dur-
ing pregnancy, remains unclear [139]. Diaz-Gomez et al [139]
observed that even if no significant differences were deter-
mined between maternal groups, neonates of smoking
mothers had significantly lower serum 25(OH)D concentra-
tions than neonates of nonsmokers (35.5 ± 15.5 nmol/L vs
55.8 ± 28.3 nmol/L, respectively; P = .009). Neonates of
smoking mothers were also significantly smaller than neo-
nates of nonsmoking mothers (2938 ± 465 g vs 3358 ± 456 g,
P = .001) [139]. Dodds and colleagues showed a relationship
between smoking in pregnancy and VitD deficiency (OR [95%
CI]) of 3.73 (1.95-7.14) [134]. It is unclear if lower maternal and/
or neonatal 25(OH)D concentrations are caused by smoke or
other co-associating factors such as supplement use, sun
exposure, and others. However, chemicals from second-hand
smoke can be passed to the fetus through the placenta [140],
and nicotine has the effect of decreasing blood flow to the
fetus [141]. This could potentially decrease the transfer of 25
(OH)D from mother to child.
4.9.2. Use of medications
Several drugs can interfere with VitD metabolism, including
antiepileptic drugs, glucocorticoids, bisphosphonates, antiretro-
viral drugs, antiestrogen drugs, and antihypertensive drugs [142].
As adequate 25(OH)D concentrations are important for maternal
and neonatal stores and health, the use of these drugs during
pregnancy can be critical. Unfortunately, there is scarcity of data
on this topic, and further investigation on the subject is required.
5. Knowledge gaps
Several knowledge gaps are highlighted in this review; for
instance, data are available on the relationship between
maternal risk factors and their relative importance. However,
16 N U TR IT ION RE S EA R CH 63 ( 20 1 9 ) 1 – 2 0
knowledge gaps exist between some maternal risk factors and
neonatal VitD status. Addressing the following research gaps
will be of value:
• The impact of pregnancy comorbidities like GDM and PIH
on neonatal VitD status.
• The use of medications that interfere with VitD metabolism
in pregnancy and the effects on maternal-fetal VitD status.
• Explore the genetic disparities among different ethnicities
for VitD production and concentrations.
• Identify the confounding contributors to the high preva-
lence of VitD deficiency among pregnant women who are
newly immigrated to the temperate latitudes.
• The total maternal VitD intake that is consistent with
healthy targets for neonatal VitD status.
6. Summary and conclusion
According to the scientific evidence summarized in this
literature review, major maternal risk factors related to low
25(OH)D concentrations in North American newborns are low
maternal 25(OH)D concentrations, inadequate VitD supple-
ment use, and intermediate or dark skin pigmentation.
Although black ethnicity came out as a major risk factor for
low 25(OH)D concentrations, it was difficult to tease out the
extent of the contribution of genetics, clothing style, SES, and
cultural practices. Moderate risk factors include low SES and
low education levels, GDM, PIH, seasonal variations, high
maternal BMI, smoking or exposure to smoke, and no
recommendation of VitD supplementation. Living in the
temperate zone limits sun exposure because of winter
months and latitude, which can reduce the production of
endogenous VitD synthesis. In Canada and the United States,
VitD testing is not routinely undertaken during pregnancy or
at birth because of its relatively high cost compared to
supplementation, but it is pertinent that health care providers
know the risk factors for low VitD status, including the
importance of supplementation and adherence.
Acknowledgment
This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors.
The authors declare no conflict of interest.
REFERENCES
[1] Wagner CL, Greer FR. Prevention of rickets and vitamin D
deficiency in infants, children, and adolescents. Pediatrics
2008;122:1142–52.
[2] Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM,
Clinton SK, et al. The 2011 dietary reference intakes for
calcium and vitamin D: what dietetics practitioners need to
know. J Am Diet Assoc 2011;111:524–7.
[3] Ross AC, Taylor CL, Yaktine AL, Valle HBD. Dietary reference
intakes for calcium and vitamin D. National Academies
Press; 2011.
[4] Hazell TJ, Gallo S, Berzina I, Vanstone CA, Rodd C, Weiler
HA. Plasma 25-hydroxyvitamin D, more so than its epimer,
has a linear relationship to leaner body composition across
infancy in healthy term infants. Appl Physiol Nutr Metab
2014;39:1137–43.
[5] Crozier SR, Harvey NC, Inskip HM, Godfrey KM, Cooper C,
Robinson SM, et al. Maternal vitamin D status in pregnancy
is associated with adiposity in the offspring: findings from
the Southampton Women's Survey. Am J Clin Nutr 2012;96:
57–63.
[6] Harvey NC, Moon RJ, Sayer AA, Ntani G, Davies JH, Javaid
MK, et al. Maternal antenatal vitamin D status and offspring
muscle development: findings from the Southampton
Women's survey. J Clin Endocrinol Metab 2014;99:330–7.
[7] Hollis BW, Wagner CL. Vitamin D and pregnancy: skeletal
effects, nonskeletal effects, and birth outcomes. Calcif
Tissue Int 2013;92:128–39.
[8] Kovacs CS, Kronenberg HM. Maternal-fetal calcium and
bone metabolism during pregnancy, puerperium, and lac-
tation. Endocr Rev 1997;18:832–72.
[9] Mulligan ML, Felton SK, Riek AE, Bernal-Mizrachi C. Impli-
cations of vitamin D deficiency in pregnancy and lactation.
Am J Obstet Gynecol 2010;202:429.e1-9.
[10] Wagner CL, Taylor SN, Johnson DD, Hollis BW. The role of
vitamin D in pregnancy and lactation: emerging concepts.
Womens Health (Lond) 2012;8:323–40.
[11] Kovacs CS. Maternal mineral and bone metabolism during
pregnancy, lactation, and post-weaning recovery. Physiol
Rev 2016;96:449–547.
[12] White P, Cooke N. The multifunctional properties and
characteristics of vitamin D-binding protein. Trends
Endocrinol Metab 2000;11:320–7.
[13] Institute of Medicine (US) Committee to Review Dietary
Reference Intakes for Vitamin D and Calcium. Overview of
vitamin D. In: Ross AC, Taylor CL, Yaktine AL, Del Valle HB,
editors. Dietary reference intakes for calcium and vitamin D.
Washington (DC); 2011.
[14] Woolcott CG, Giguère Y, Weiler HA, Spencer A, Forest J-C,
Armson BA, et al. Determinants of vitamin D status in
pregnant women and neonates. Can J Public Health 2016;
107:410–6.
[15] Aghajafari F, Field CJ, Kaplan BJ, Maggiore JA, O'Beirne M,
Hanley DA, et al. The high prevalence of vitamin D
insufficiency in cord blood in Calgary, Alberta (APrON-D
Study). J Obstet Gynaecol Can 2017;39:347-53.e1.
[16] Bodnar LM, Simhan HN, Powers RW, Frank MP, Cooperstein
E, Roberts JM. High prevalence of vitamin D insufficiency in
black and white pregnant women residing in the northern
United States and their neonates. J Nutr 2007;137:447–52.
[17] Canadian Paediatric Society. Vitamin D: caring for kids.
http://www.caringforkids.cps.ca/handouts/vitamin_d; 2012,
Accessed date: 16 May 2016.
[18] Godel JC, Irvine J, Onyett H, Saylor K, Schroter H, Young M,
Wong S. Vitamin D supplementation: recommendations for
Canadian mothers and infants. Paediatr Child Health 2007;
12:583–98.
[19] Dror DK, Allen LH. Vitamin D inadequacy in pregnancy: biology,
outcomes, and interventions. Nutr Rev 2010;68:465–77.
[20] Jacquemyn Y, Ajaji M, Karepouan N. Vitamin D levels in
maternal serum and umbilical cord blood in a multi-ethnic
population in Antwerp, Belgium. Facts Views Vis Obgyn
2013;5:3–5.
[21] Godang K, Froslie KF, Henriksen T, Qvigstad E, Bollerslev J.
Seasonal variation in maternal and umbilical cord 25(OH)
vitamin D and their associations with neonatal adiposity.
Eur J Endocrinol 2014;170:609–17.
[22] Mahon P, Harvey N, Crozier S, Inskip H, Robinson S, Arden N,
et al. Low maternal vitamin D status and fetal bone
development: cohort study. J Bone Miner Res 2010;25:14–9.
 N U TR IT ION RE S EA R CH 6 3 ( 20 1 9 ) 1– 2 0
[23] Tobias JH, Cooper C. Perspective: PTH/PTHrP activity and the
programming of skeletal development in utero. J Bone Miner
Res 2004;19:177–82.
[24] Balasubramanian S. Vitamin D deficiency in breastfed
infants & the need for routine vitamin D supplementation.
Indian J Med Res 2011;133:250–2.
[25] Weiler H. Vitamin D: the current state in Canada. https://
www.cfdr.ca/Downloads/CCFN-docs/Watching-Brief-on-
Vitamin-D—final—Aug3-08-revA.aspx; 2008, Accessed date:
12 March 2016.
[26] Ward LM, Gaboury I, Ladhani M, Zlotkin S. Vitamin D-
deficiency rickets among children in Canada. CMAJ 2007;
177:161–6.
[27] CDC. Centers for Disease Control and Prevention identifies
nutritional deficiencies among young children. https://
www.cdc.gov/media/pressrel/r010330.htm; 2001, Accessed
date: 5 May 2017.
[28] Weisberg P, Scanlon KS, Li R, Cogswell ME. Nutritional
rickets among children in the United States: review of cases
reported between 1986 and 2003. Am J Clin Nutr 2004;80
[1697S-705S].
[29] Robinson CJ, Wagner CL, Hollis BW, Baatz JE, Johnson DD.
Maternal vitamin D and fetal growth in early-onset severe
preeclampsia. Am J Obstet Gynecol 2011;204:556.e1-4.
[30] Leffelaar ER, Vrijkotte TG, van Eijsden M. Maternal early
pregnancy vitamin D status in relation to fetal and neonatal
growth: results of the multi-ethnic Amsterdam born children
and their development cohort. Br J Nutr 2010;104:108–17.
[31] Aghajafari F, Nagulesapillai T, Ronksley PE, Tough SC,
O'Beirne M, Rabi DM. Association between maternal serum
25-hydroxyvitamin D level and pregnancy and neonatal
outcomes: systematic review and meta-analysis of obser-
vational studies. BMJ 2013;346:f1169.
[32] Wagner C, Baggerly C, McDonnell S, Baggerly K, French C,
Baggerly L, et al. Post-hoc analysis of vitamin D status and
reduced risk of preterm birth in two vitamin D pregnancy
cohorts compared with South Carolina March of Dimes
2009-2011 rates. J Steroid Biochem Mol Biol 2016;155:245–51.
[33] McDonnell SL, Baggerly KA, Baggerly CA, Aliano JL, French
CB, Baggerly LL, et al. Maternal 25 (OH) D concentrations≥ 40
ng/mL associated with 60% lower preterm birth risk among
general obstetrical patients at an urban medical center.
PLoS One 2017;12:e0180483.
[34] Bowyer L, Catling-Paull C, Diamond T, Homer C, Davis G,
Craig ME. Vitamin D, PTH and calcium levels in pregnant
women and their neonates. Clin Endocrinol 2009;70:372–7.
[35] Eckhardt CL, Gernand AD, Roth DE, Bodnar LM. Maternal
vitamin D status and infant anthropometry in a US multi-
centre cohort study. Ann Hum Biol 2015;42:215–22.
[36] Weiler H, Fitzpatrick-Wong S, Veitch R, Kovacs H,
Schellenberg J, McCloy U, et al. Vitamin D deficiency and
whole-body and femur bone mass relative to weight in
healthy newborns. CMAJ 2005;172:757–61.
[37] Camargo Jr CA, Rifas-Shiman SL, Litonjua AA, Rich-Edwards
JW, Weiss ST, Gold DR, et al. Maternal intake of vitamin D
during pregnancy and risk of recurrent wheeze in children
at 3 y of age. Am J Clin Nutr 2007;85:788–95.
[38] Erkkola M, Nwaru BI, Viljakainen HT. Maternal vitamin D
during pregnancy and its relation to immune-mediated
diseases in the offspring. Vitam Horm 2011;86:239–60.
[39] Wolsk HM, Harshfield BJ, Laranjo N, Carey VJ, O'Connor G,
Sandel M, et al. Vitamin D supplementation in pregnancy,
prenatal 25 (OH) D levels, race, and subsequent asthma or
recurrent wheeze in offspring: secondary analyses from the
Vitamin D Antenatal Asthma Reduction Trial. J Allergy Clin
Immunol 2017;140:1423-9.e5.
[40] Lee JM, Smith JR, Philipp BL, Chen TC, Mathieu J, Holick MF.
Vitamin D deficiency in a healthy group of mothers and
newborn infants. Clin Pediatr (Phila) 2007;46:42–4.
17
[41] Bodnar LM, Catov JM, Roberts JM, Simhan HN. Prepregnancy
obesity predicts poor vitamin D status in mothers and their
neonates. J Nutr 2007;137:2437–42.
[42] Dror DK, King JC, Durand DJ, Allen LH. Association of
modifiable and nonmodifiable factors with vitamin D status
in pregnant women and neonates in Oakland, CA. J Am Diet
Assoc 2011;111:111–6.
[43] Martin-Gronert MS, Ozanne SE. Maternal nutrition during
pregnancy and health of the offspring. Biochem Soc Trans
2006;34:779–82.
[44] Rush D. Nutrition and maternal mortality in the developing
world. Am J Clin Nutr 2000;72:212S-40S.
[45] Bhutta ZA, Das JK, Rizvi A, Gaffey MF, Walker N, Horton S,
et al. Evidence-based interventions for improvement of
maternal and child nutrition: what can be done and at what
cost? Lancet 2013;382:452–77.
[46] Health Canada. Vitamin D and calcium: updated dietary
reference intakes. http://www.hc-sc.gc.ca/fn-an/nutrition/
vitamin/vita-d-eng.php#a10; 2012, Accessed date: 17 May 2017.
[47] Rovner AJ, O'Brien KO. Hypovitaminosis D among healthy
children in the United States: a review of the current
evidence. Arch Pediatr Adolesc Med 2008;162:513–9.
[48] Spiro A, Buttriss JL. Vitamin D: An overview of vitamin D
status and intake in Europe. Nutr Bull 2014;39:322–50.
[49] 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.
[50] Holick MF. Vitamin D status: measurement, interpretation,
and clinical application. Ann Epidemiol 2009;19:73–8.
[51] Gallo S, Hazell T, Vanstone CA, Agellon S, Jones G, L'Abbe M,
et al. Vitamin D supplementation in breastfed infants from
Montreal, Canada: 25-hydroxyvitamin D and bone health
effects from a follow-up study at 3 years of age. Osteoporos
Int 2016;27:2459–66.
[52] Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley
DA, Heaney RP, et al. Evaluation, treatment, and prevention of
vitamin D deficiency: an Endocrine Society clinical practice
guideline. J Clin Endocrinol Metab 2011;96:1911–30.
[53] Hayes A, Cashman KD. Food-based solutions for vitamin D
deficiency: putting policy into practice and the key role for
research. Proc Nutr Soc 2017;76:54–63.
[54] Pilz S, März W, Cashman KD, Kiely ME, Whiting SJ, Holick
MF, et al. Rationale and plan for vitamin D food fortification:
a review and guidance paper. Front Endocrinol 2018;9:373.
[55] Health Canada. Prenatal nutrition guidelines for health
professionals—background on Canada's food guide. http://
www.hc-sc.gc.ca/fn-an/pubs/nutrition/guide-prenatal-eng.
php; 2010, Accessed date: 13 May 2016.
[56] World Health Organization. Guideline: daily iron and folic
acid supplementation in pregnant women. http://apps.who.
int/iris/bitstream/10665/77770/1/9789241501996_eng.pdf;
2012, Accessed date: 13 March 2017.
[57] National Institute of Diabetes and Digestive and Kidney
Diseases. Fit for two—tips for pregnancy. https://www.
niddk.nih.gov/health-information/health-topics/weight-
control/tips-for-two-pregnancy/Pages/fit-for-two.aspx;
2013, Accessed date: 12 June 2016.
[58] UNICEF, World Health Organization, United Nations
University. Composition of a multi-micronutrient supple-
ment to be used in pilot programmes among pregnant
women in developing countries: report of a United Nations
Children's Fund (UNICEF), World Health Organization (WHO),
United Nations University workshop; 1999. http://www.who.
int/iris/handle/10665/75358, Accessed date: 13 March 2018.
[59] Wood CL, Cheetham TD. Vitamin D: increasing supplement
use among at-risk groups (NICE guideline PH56). Arch Dis
Child Educ Pract Ed 2016;101:43–5.
[60] Office of Kids and Families. Having a baby. Australia: New
South Wales Government; 2012.
18 N U TR IT ION RE S EA R CH 63 ( 20 1 9 ) 1 – 2 0
[61] Kaiser L, Allen LH. Position of the American Dietetic
Association: nutrition and lifestyle for a healthy pregnancy
outcome. J Am Diet Assoc 2008;108:553–61.
[62] Munns CF, Shaw N, Kiely M, Specker BL, Thacher TD, Ozono
K, et al. Global consensus recommendations on prevention
and management of nutritional rickets. J Clin Endocrinol
Metab 2016;101:394–415.
[63] ACOG Committee On obstetric practice. ACOG Committee
opinion no. 495: vitamin D: screening and supplementation
during pregnancy. Obstet Gynecol 2011;118:197–8.
[64] Calvo MS, Whiting SJ, Barton CN. Vitamin D fortification in
the United States and Canada: current status and data
needs. Am J Clin Nutr 2004;80:1710S-6S.
[65] Morisset AS, Weiler HA, Dubois L, Ashley-Martin J, Shapiro
GD, Dodds L, et al. Rankings of iron, vitamin D, and calcium
intakes in relation to maternal characteristics of pregnant
Canadian women. Appl Physiol Nutr Metab 2016;41:749–57.
[66] Aghajafari F, Field CJ, Kaplan BJ, Rabi DM, Maggiore JA,
O'Beirne M, et al. The current recommended vitamin D
intake guideline for diet and supplements during pregnancy
is not adequate to achieve vitamin D sufficiency for most
pregnant women. PLoS One 2016;11:e0157262.
[67] Ginde AA, Sullivan AF, Mansbach JM, Camargo Jr CA.
Vitamin D insufficiency in pregnant and nonpregnant
women of childbearing age in the United States. Am J Obstet
Gynecol 2010;202:436.e1-8.
[68] Palacios C, De-Regil LM, Lombardo LK, Pena-Rosas JP.
Vitamin D supplementation during pregnancy: updated
meta-analysis on maternal outcomes. J Steroid Biochem
Mol Biol 2016;164:148–55.
[69] Hollis BW, Johnson D, Hulsey TC, Ebeling M, Wagner CL.
Vitamin D supplementation during pregnancy: double-
blind, randomized clinical trial of safety and effectiveness. J
Bone Miner Res 2011;26:2341–57.
[70] Grant CC, Stewart AW, Scragg R, Milne T, Rowden J, Ekeroma
A, et al. Vitamin D during pregnancy and infancy and infant
serum 25-hydroxyvitamin D concentration. Pediatrics 2014;
133:e143–53.
[71] Perumal N, Al Mahmud A, Baqui AH, Roth DE. Prenatal
vitamin D supplementation and infant vitamin D status in
Bangladesh. Public Health Nutr 2017;20:1865–73.
[72] Sablok A, Batra A, Thariani K, Batra A, Bharti R, Aggarwal
AR, et al. Supplementation of vitamin D in pregnancy and
its correlation with feto-maternal outcome. Clin Endocrinol
2015;83:536–41.
[73] Abrams SA, Hawthorne KM, Rogers SP, Hicks PD, Carpenter
TO. Effects of ethnicity and vitamin D supplementation on
vitamin D status and changes in bone mineral content in
infants. BMC Pediatr 2012;12:6.
[74] Wagner CL, McNeil R, Hamilton SA, Winkler J, Rodriguez
Cook C, Warner G, et al. A randomized trial of vitamin D
supplementation in 2 community health center networks in
South Carolina. Am J Obstet Gynecol 2013;208:137.e1-13.
[75] Hossain N, Kanani FH, Ramzan S, Kausar R, Ayaz S, Khanani R,
et al. Obstetric and neonatal outcomes of maternal vitamin D
supplementation: results of an open-label, randomized
controlled trial of antenatal vitamin D supplementation in
Pakistani women. J Clin Endocrinol Metab 2014;99:2448–55.
[76] Bi WG, Nuyt AM, Weiler H, Leduc L, Santamaria C, Wei SQ.
Association between vitamin D supplementation during preg-
nancy and offspring growth, morbidity, and mortality: a sys-
tematic review and meta-analysis. JAMA Pediatr 2018;172:635–45.
[77] Picciano MF, Dwyer JT, Radimer KL, Wilson DH, Fisher KD,
Thomas PR, et al. Dietary supplement use among infants,
children, and adolescents in the United States, 1999-2002.
Arch Pediatr Adolesc Med 2007;161:978–85.
[78] Ahrens KA, Rossen LM, Simon AE. Adherence to vitamin D
recommendations among US infants aged 0 to 11 months,
NHANES, 2009 to 2012. Clin Pediatr 2016;55:555–6.
[79] American Academy of Pediatrics. A supplement of 400 IU
per day of vitamin D is recommended for all breastfed
infants. https://www.cdc.gov/breastfeeding/
recommendations/vitamin_d.htm; 2008, Accessed date: 22
April 2016.
[80] Perrine CG, Sharma AJ, Jefferds ME, Serdula MK, Scanlon KS.
Adherence to vitamin D recommendations among US
infants. Pediatrics 2010;125:627–32.
[81] Canada S. Table 13-10-0793-01 types of nutrients from
nutritional supplements—consumed in the past month, by
age group and sex, household population aged 1 and over,
Canadian Community Health Survey (CCHS)–Nutrition,
Canada. https://www150.statcan.gc.ca/t1/tbl1/en/cv.action;
2015, Accessed date: 29 June 2018.
[82] Jasti S, Siega-Riz AM, Cogswell ME, Hartzema AG, Bentley
ME. Pill count adherence to prenatal multivitamin/mineral
supplement use among low-income women. J Nutr 2005;
135:1093–101.
[83] Health Canada. Vitamin D supplementation of breastfed
infants in Canada: key statistics and graphics (2009-2010).
http://www.hc-sc.gc.ca/fn-an/surveill/nutrition/commun/
prenatal/vit_d_sup-eng.php; 2012, Accessed date: 3 May
2016.
[84] Nechitilo M, Nguyen P, Webb-Girard A, Gonzalez-Casanova
I, Martorell R, DiGirolamo A, et al. A qualitative study of
factors influencing initiation and adherence to micronutri-
ent supplementation among women of reproductive age in
Vietnam. Food Nutr Bull 2016;37:461–74.
[85] Toher C, Lindsay K, McKenna M, Kilbane M, Curran S,
Harrington L, et al. Relationship between vitamin D knowl-
edge and 25-hydroxyvitamin D levels amongst pregnant
women. J Hum Nutr Diet 2014;27:261–9.
[86] Awker AL, Herbranson AT, Rhee TG, Westberg SM. Impact of
a vitamin D protocol in pregnancy at an urban women's
health clinic. Ann Pharmacother 2016;50:935–41.
[87] Kramer CK, Ye C, Swaminathan B, Hanley AJ, Connelly PW,
Sermer M, et al. The persistence of maternal vitamin D
deficiency and insufficiency during pregnancy and lactation
irrespective of season and supplementation. Clin
Endocrinol 2016;84:680–6.
[88] 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.
[89] 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.
[90] Nicolaidou P, Hatzistamatiou Z, Papadopoulou A, Kaleyias J,
Floropoulou E, Lagona E, et al. Low vitamin D status in
mother-newborn pairs in Greece. Calcif Tissue Int 2006;78:
337–42.
[91] Hollis BW, Wagner CL. Nutritional vitamin D status during
pregnancy: reasons for concern. CMAJ 2006;174:1287–90.
[92] Matsuoka LY, Wortsman J, Haddad JG, Kolm P, Hollis BW.
Racial pigmentation and the cutaneous synthesis of vitamin
D. Arch Dermatol 1991;127:536–8.
[93] Marcus R, Feldman D, Nelson D, Rosen CJ. Fundamentals of
osteoporosis. Elsevier Science; 2009.
[94] Powe CE, Evans MK, Wenger J, Zonderman AB, Berg AH,
Nalls M, et al. Vitamin D-binding protein and vitamin D
status of black Americans and white Americans. N Engl J
Med 2013;369:1991–2000.
[95] Martin CA, Gowda U, Renzaho AM. The prevalence of
vitamin D deficiency among dark-skinned populations
according to their stage of migration and region of birth: a
meta-analysis. Nutrition 2016;32:21–32.
[96] Gangat M, Ponnapakkam T, Bradford E, Katikaneni R, Gensure
R. Reversed seasonal variation in maternal vitamin D levels in
southern Louisiana. Clin Pediatr (Phila) 2012;51:718–22.
 N U TR IT ION RE S EA R CH 6 3 ( 20 1 9 ) 1– 2 0
[97] Hoath SB, Maibach HI. Neonatal skin: structure and func-
tion. Taylor & Francis; 2003.
[98] Walsh R. Variation in the melanin content of the skin of
New Guinea natives at different ages. J Invest Dermatol
1964;42:261–5.
[99] Cuhaci-Cakir B, Demirel F. Effects of seasonal variation and
maternal clothing style on vitamin D levels of mothers and
their infants. Turk J Pediatr 2014;56:475–81.
[100] Dijkstra SH, van Beek A, Janssen JW, de Vleeschouwer LH,
Huysman WA, van den Akker EL. High prevalence of
vitamin D deficiency in newborn infants of high-risk
mothers. Arch Dis Child 2007;92:750–3.
[101] Davenport ML, Uckun A, Calikoglu AS. Pediatrician patterns
of prescribing vitamin supplementation for infants: do they
contribute to rickets? Pediatrics 2004;113:179–80.
[102] Shaikh U, Alpert PT. Practices of vitamin D recommendation
in Las Vegas, Nevada. J Hum Lact 2004;20:56–61.
[103] Taylor JA, Geyer LJ, Feldman KW. Use of supplemental
vitamin D among infants breastfed for prolonged periods.
Pediatrics 2010;125:105–11.
[104] World Health Organization. Infant and young child feeding :
model chapter for textbooks for medical students and allied
health professionals. WHO Library Cataloguing-in-
Publication Data; 2009.
[105] Sherman EM, Svec RV. Barriers to vitamin D supplementa-
tion among military physicians. Mil Med 2009;174:302–7.
[106] Li W, Green TJ, Innis SM, Barr SI, Whiting SJ, Shand A, et al.
Suboptimal vitamin D levels in pregnant women despite
supplement use. Can J Public Health 2011;102:308–12.
[107] Statistics Canada. Median total income, by family type, by
province and territory (all census families). http://www.
statcan.gc.ca/tables-tableaux/sum-som/l01/cst01/
famil108a-eng.htm; 2015, Accessed date: 12 March 2018.
[108] Grant WB, Schwalfenberg GK, Genuis SJ, Whiting SJ. An
estimate of the economic burden and premature deaths due
to vitamin D deficiency in Canada. Mol Nutr Food Res 2010;
54:1172–81.
[109] Wagner CL, McNeil RB, Johnson DD, Hulsey TC, Ebeling M,
Robinson C, et al. Health characteristics and outcomes of
two randomized vitamin D supplementation trials during
pregnancy: a combined analysis. J Steroid Biochem Mol Biol
2013;136:313–20.
[110] Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF.
Decreased bioavailability of vitamin D in obesity. Am J Clin
Nutr 2000;72:690–3.
[111] Cheng S, Massaro JM, Fox CS, Larson MG, Keyes MJ, McCabe EL,
et al. Adiposity, cardiometabolic risk, and vitamin D status: the
Framingham heart study. Diabetes 2010;59:242–8.
[112] Josefson JL, Reisetter A, Scholtens DM, Price HE, Metzger BE,
Langman CB, et al. Maternal BMI associations with maternal
and cord blood vitamin D levels in a North American subset
of Hyperglycemia and Adverse Pregnancy Outcome (HAPO)
study participants. PLoS One 2016;11:e0150221.
[113] Dietitians of Canada. BMI for adults. http://www.dietitians.
ca/your-health/assess-yourself/assess-your-bmi/bmi-adult.
aspx; 2016, Accessed date: 14 June 2016.
[114] Evans KN, Bulmer JN, Kilby MD, Hewison M. Vitamin D and
placental-decidual function. J Soc Gynecol Investig 2004;11:
263–71.
[115] Cardus A, Parisi E, Gallego C, Aldea M, Fernandez E,
Valdivielso JM. 1,25-dihydroxyvitamin D-3 stimulates vas-
cular smooth muscle cell proliferation through a VEGF-
mediated pathway. Kidney Int 2006;69:1377–84.
[116] Aranow C. Vitamin D and the immune system. J Investig
Med 2011;59:881–6.
[117] Li YC, Kong J, Wei MJ, Chen ZF, Liu SQ, Cao LP. 1,25-
Dihydroxyvitamin D-3 is a negative endocrine regulator of
the renin-angiotensin system. J Clin Invest 2002;110:229–38.
19
[118] Bodnar LM, Catov JM, Simhan HN, Holick MF, Powers RW,
Roberts JM. Maternal vitamin D deficiency increases the risk
of preeclampsia. J Clin Endocrinol Metab 2007;92:3517–22.
[119] Achkar M, Dodds L, Giguere Y, Forest JC, Armson BA,
Woolcott C, et al. Vitamin D status in early pregnancy and
risk of preeclampsia. Am J Obstet Gynecol 2015;212:511.e1-7.
[120] Baker AM, Haeri S, Camargo Jr CA, Espinola JA, Stuebe AM. A
nested case-control study of midgestation vitamin D
deficiency and risk of severe preeclampsia. J Clin Endocrinol
Metab 2010;95:5105–9.
[121] Rostami M, Ramezani Tehrani F, Simbar M, Bidhendi
Yarandi R, Minooee S, Hollis BW, et al. Effectiveness of
prenatal vitamin D deficiency screening and treatment
program: a stratified randomized field trial. J Clin Endocrinol
Metab 2018;103:2936–48.
[122] Mirzakhani H, Litonjua AA, McElrath TF, O'Connor G, Lee-
Parritz A, Iverson R, et al. Early pregnancy vitamin D status
and risk of preeclampsia. J Clin Invest 2016;126:4702–15.
[123] Ali AM, Alobaid A, Malhis TN, Khattab AF. Effect of vitamin
D3 supplementation in pregnancy on risk of pre-eclampsia
—randomized controlled trial. Clin Nutr 2018. https://doi.
org/10.1016/j.clnu.2018.02.023 [in Press].
[124] Behjat Sasan S, Zandvakili F, Soufizadeh N, Baybordi E. The
effects of vitamin D supplement on prevention of recur-
rence of preeclampsia in pregnant women with a history of
preeclampsia. Obstet Gynecol Int 2017;2017. https://doi.org/
10.1155/2017/8249264.
[125] Wei SQ, Qi HP, Luo ZC, Fraser WD. Maternal vitamin D status
and adverse pregnancy outcomes: a systematic review and
meta-analysis. J Matern Fetal Neonatal Med 2013;26:889–99.
[126] Organization WH. WHO recommendations for prevention
and treatment of pre-eclampsia and eclampsia. http://apps.
who.int/iris/bitstream/handle/10665/44703/9789241548335_
eng.pdf;jsessionid=AE4940D67F2746CCE33DE3EE12713076?
sequence=1; 2011, Accessed date: 13 April 2016.
[127] Bellamy L, Casas JP, Hingorani AD, Williams D. Type 2
diabetes mellitus after gestational diabetes: a systematic
review and meta-analysis. Lancet 2009;373:1773–9.
[128] Chiu KC, Chu A, Go VLW, Saad MF. Hypovitaminosis D is
associated with insulin resistance and beta cell dysfunction.
Am J Clin Nutr 2004;79:820–5.
[129] Clifton-Bligh RJ, McElduff P, McElduff A. Maternal vitamin D
deficiency, ethnicity and gestational diabetes. Diabet Med 2008;
25:678–84.
[130] Farrant HJW, Krishnaveni GV, Hill JC, Boucher BJ, Fisher DJ,
Noonan K, et al. Vitamin D insufficiency is common in Indian
mothers but is not associated with gestational diabetes or
variation in newborn size. Eur J Clin Nutr 2009;63:646–52.
[131] Makgoba M, Nelson SM, Savvidou M, Messow CM, Nicolaides
K, Sattar N. First-trimester circulating 25-hydroxyvitamin D
levels and development of gestational diabetes mellitus.
Diabetes Care 2011;34:1091–3.
[132] Parlea L, Bromberg I, Feig D, Vieth R, Merman E, Lipscombe L.
Association between serum 25-hydroxyvitamin D in early
pregnancy and risk of gestational diabetes mellitus. Diabet Med
2012;29:e25–32.
[133] Lacroix M, Battista MC, Doyon M, Houde G, Menard J,
Ardilouze JL, et al. Lower vitamin D levels at first trimester
are associated with higher risk of developing gestational
diabetes mellitus. Acta Diabetol 2014;51:609–16.
[134] Dodds L, Woolcott CG, Weiler H, Spencer A, Forest JC,
Armson BA, et al. Vitamin D status and gestational diabetes:
effect of smoking status during pregnancy. Paediatr Perinat
Epidemiol 2016;30:229–37.
[135] Soheilykhah S, Mojibian M, Moghadam MJ, Shojaoddiny-
Ardekani A. The effect of different doses of vitamin D
supplementation on insulin resistance during pregnancy.
Gynecol Endocrinol 2013;29:396–9.
20 N U TR IT ION RE S EA R CH 63 ( 20 1 9 ) 1 – 2 0
[136] Karamali M, Asemi Z, Ahmadi-Dastjerdi M, Esmaillzadeh A.
Calcium plus vitamin D supplementation affects preg-
nancy outcomes in gestational diabetes: randomized,
double-blind, placebo-controlled trial. Public Health Nutr
2016;19:156–63.
[137] Weinert LS, Reichelt AJ, Schmitt LR, Boff R, Oppermann MLR,
Camargo JL, et al. Vitamin D deficiency increases the risk of
adverse neonatal outcomes in gestational diabetes. PLoS
One 2016;11:e0164999.
[138] Asemi Z, Karamali M, Esmaillzadeh A. Favorable effects of
vitamin D supplementation on pregnancy outcomes in
gestational diabetes: a double blind randomized controlled
clinical trial. Horm Metab Res 2015;47:565–70.
[139] Diaz-Gomez NM, Mendoza C, Gonzalez-Gonzalez NL,
Barroso F, Jimenez-Sosa A, Domenech E, et al. Maternal
smoking and the vitamin D-parathyroid hormone
system during the perinatal period. J Pediatr 2007;151:
618–23.
[140] U.S. Department of Health and Human Services, Centres for
Disease Control and Prevention, National Center for Chronic
Disease Prevention and Health Promotion, Office on
Smoking an Health. The health consequences of involun-
tary exposure to tobacco smoke. A report of the Surgeon
General. http://www.surgeongeneral.gov/library/
secondhandsmoke/index.html; 2006, Accessed date: 13
April 2016.
[141] U.S. Department of Health and Human Services, Centers for
Disease Control and Prevention, National Center for Chronic
Disease Prevention and Health Promotion, Office on
Smoking and Health. A report of the Surgeon General: how
tobacco smoke causes disease the biology and behavioral
basis for smoking-attributable disease. http://www.
surgeongeneral.gov/library/tobaccosmoke/report/chapter8.
pdf; 2010, Accessed date: 13 April 2016.
[142] Grober U, Kisters K. Influence of drugs on vitamin D and
calcium metabolism. Dermatoendocrinol 2012;4:158–66.
[143] Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM,
Clinton SK, et al. The 2011 report on dietary reference
intakes for calcium and vitamin D from the Institute of
Medicine: what clinicians need to know. J Clin Endocrinol
Metab 2011;96:53–8.
[144] Aspray TJ, Bowring C, Fraser W, Gittoes N, Javaid MK,
Macdonald H, et al. National Osteoporosis Society vitamin D
guideline summary. Age Ageing 2014;43:592–5.
[145] Pludowski P, Karczmarewicz E, Bayer M, Carter G, Chlebna-
Sokol D, Czech-Kowalska J, et al. Practical guidelines for the
supplementation of vitamin D and the treatment of deficits
in Central Europe—recommended vitamin D intakes in the
general population and groups at risk of vitamin D
deficiency. Endokrynol Pol 2013;64:319–27.
[146] German Nutrition S. New reference values for vitamin D.
Ann Nutr Metab 2012;60:241–6.
[147] Nordic Council of Ministers. Nordic nutrition recommenda-
tions 2012. Integrating nutrition and physical activity.
http://www.norden.org/en/theme/former-themes/themes-
2016/nordic-nutrition-recommendation/nordic-nutrition-
recommendations-2012; 2014, Accessed date: 13 April 2016.
[148] Health Council of the Netherlands. Evaluation of dietary
reference values for vitamin D. https://www.
gezondheidsraad.nl/en/task-and-procedure/areas-of-
activity/healthy-nutrition/evaluation-of-the-dietary-
reference-values; 2012, Accessed date: 13 April 2016.
[149] Nowson CA, McGrath JJ, Ebeling PR, Haikerwal A, Daly RM,
Sanders KM, et al. Vitamin D and health in adults in
Australia and New Zealand: a position statement. Med J
Aust 2012;196:686–7.
[150] Diamond TH, Eisman JA, Mason RS, Nowson CA, Pasco JA,
Sambrook PN, et al. Vitamin D and adult bone health in
Australia and New Zealand: a position statement. Med J Aust
2005;182:281–5.
[151] Dror DK, King JC, Fung EB, Loan MDV, Gertz ER, Allen LH.
Evidence of associations between feto-maternal vitamin D
status, cord parathyroid hormone and bone-specific alka-
line phosphatase, and newborn whole body bone mineral
content. Nutrients 2012;4:68–77.
[152] Wang C, Gao JS, Yu SL, Qiu L, Zeng L, Wang DH. Correlation
between neonatal vitamin D level and maternal vitamin D
level. Zhongguo Dang Dai Er Ke Za Zhi 2016;18:20–3.
[153] Banihosseini SZ, Baheiraei A, Shirzad N, Heshmat R,
Mohsenifar A. The effect of cigarette smoke exposure on
vitamin D level and biochemical parameters of mothers and
neonates. J Diabetes Metab Disord 2013;12:19.