Medicines Q&As
Q&A 329.1
Which oral vitamin D dosing regimens correct deficiency in pregnancy?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
Before using this Q&A, read the disclaimer at www.ukmi.nhs.uk/activities/medicinesQAs/default.asp
Date prepared: January 2014
Summary
 During pregnancy, maternal vitamin D deficiency (defined here as less than 30nmol/L) can lead to deficiency in
the infant, resulting in Rickets and other skeletal abnormalities.
 Testing: There is no consensus on exactly which pregnant women to test for vitamin D deficiency. However, if a
pregnant woman is tested for deficiency and found to be deficient, then consideration should be given to
correcting this deficiency.
 Safety: Vitamin D use in human pregnancy is not associated with an increased risk of congenital malformation,
although the data are insufficient to confirm that there is unequivocally no risk. In the general population, an
upper physiological limit of 10,000units of vitamin D/day has been suggested. Above this daily dose, adverse
effects are theoretically more likely so bolus injections or oral doses of more than 10,000units per day should not
be used.
 Dose for correction (vitamin D <30nmol/L): It would be rational to use an oral dose of 4000units per day for up
to 11 weeks to provide a cumulative dose of around 300,000units in pregnancies that are in the 2nd or 3rd
trimester . Correction should begin in the 2nd or 3rd trimester because of the lack of safety or outcome data in first
trimester, and because the majority of skeletal growth and development is thought to occur in the 2nd or 3rd
trimester.
 Dose for rapid correction: There is no consensus on what constitutes a very low vitamin D level, but a level of
less than 15nmol/L, for example, would be considered as being very low by most clinicians. If the baseline vitamin
D level is very low and the woman is in the 2nd or 3rd trimester of her pregnancy, then rapid correction may be
required particularly if there are unmodifiable risk factors. In these cases it would be rational to use doses higher
than 4000units/day (but not more than 10,000units/day) in the second or third trimesters (e.g. 7,000units/day for
6-7 weeks or 10,000units/day for 4-5 weeks to provide a cumulative dose of around 300,000 units). However, the
higher doses should only be used with the input of an obstetrician and with monitoring of calcium levels. Large
single doses of up to 120,000 units have been used from the 5th month of pregnancy onwards; but these large
doses will only increase vitamin D levels for around 3 months and may need to be repeated.
 Other factors: When choosing a regimen, prescribers should also take into account: the severity of deficiency at
baseline; whether unmodifiable risk factors (such as covering of the skin for religious/cultural reasons) remain an
issue; the likelihood of compliance; the time of year; planned holidays in the sun; and product availability.
 Products: Vitamin D deficiency in pregnancy should be managed with colecalciferol or ergocalciferol. There are
licensed products that enable a dosing regimen of 4000units/day to be used and do not contraindicate use in
pregnancy (e.g. five x 800units capsules of Fultium D3® or tablets of Desunin®). Products containing vitamin A
(such as Cod Liver Oil) should be avoided because this is a known teratogen.
 Monitoring: To avoid maternal (and possibly foetal or neonatal) hypercalcaemia, we suggest that pregnant
women being treated for vitamin D deficiency should have their serum calcium levels checked a month after
starting treatment and then three months later, when steady state vitamin D levels have been achieved.
Subsequent monitoring of calcium levels depends on duration of treatment and concerns about toxicity. If calcium
levels are raised, then the prescriber should review the prescription for vitamin D or reduce the dose. Routine
monitoring of vitamin D levels is not necessary but if they are re-checked, this should be 3 months after starting
therapy, when steady-state has been reached.
 Calcium intake: Pregnant women should try to maintain an adequate calcium intake (700mg/day) through their
diet.
Background
Pregnant women are at particular risk of vitamin D deficiency, with recent advice defining deficiency as being
represented by a serum 25OHD level of <30nmol/L. (1) What constitutes an adequate level in pregnancy is still
controversial and many suggest >50nmol/L to be adequate whilst some suggest >75nmol/L. (2-5)
The consequences of vitamin D deficiency during pregnancy and breast-feeding are potentially quite stark. The
developing infant is dependent on its mother for vitamin D, and since maternal vitamin D status determines the
vitamin D status of the newborn, the development of rickets and other skeletal abnormalities is possible. (2;3;6-14)
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Medicines Q&As
Human breast milk contains low levels of vitamin D even when mothers are replete – therefore a fully breast-fed
infant born to a mother who is deficient of vitamin D is likely to remain deficient and at risk of skeletal abnormalities
unless an intervention is made. (6;10;12;14;15) There is therefore a good argument and support for correction of
maternal vitamin D levels prior to and after delivery and whilst breast-feeding. (6;8;9;12) Indeed, in recent years a reemergence of rickets has been seen in the UK, with cases mainly affecting children from ethnic minorities. This reemergence is probably related to both maternal and infantile diet and lifestyle in particular groups (for example, in
women who cover their skin). (6;11;14).
In addition to the reasonably well described risks associated with vitamin D deficiency in pregnancy, observational
research also suggests links between poor vitamin D status in pregnancy and pre-eclampsia, obstetric
complications, gestational diabetes and bacterial vaginosis in the mother (16-18); transient hypocalcaemia and
tetany in the new-born (19;20); and various diseases of childhood. (9) Conversely, a number of studies have
reported that infants whose mothers had adequate vitamin D levels were larger at birth and had smaller
fontanelles.(8;10;12;15)
It is then widely accepted that for a variety of health reasons outlined above, pregnant women should have adequate
vitamin D stores for their own requirements, for their developing foetus, and to build stores for early infancy
particularly where they plan to breast-feed. Current DoH guidance makes recommendations in relation to routine
supplementation in pregnancy and breast-feeding but does not address the issue of correction of vitamin D
deficiency (i.e. 25OHD < 30nmol/L) in these situations.(13)
This Q&A addresses specifically the issues associated with vitamin D dosing in pregnancy. It does not address
identification of deficiency, and hence does not include information on screening and testing that might be necessary
to determine vitamin D status in pregnant women. There is no consensus on exactly which pregnant women to test
for vitamin D deficiency. However, if a pregnant woman is tested and found to be vitamin D deficient, then
consideration should be given to correcting this deficiency. The Q&A answers the following questions using the best
evidence we have been able to identify:
1.
2.
3.
4.
5.
6.
What dose and treatment regimen could be used to correct vitamin D deficiency in pregnancy?
When should vitamin D deficiency be corrected in pregnancy?
Are high dose regimens (i.e. Up to 300,000 units cumulatively) safe for use in pregnancy?
What available products are best to use to correct vitamin D deficiency in pregnancy?
How often should a pregnant woman being treated for vitamin D deficiency be monitored?
What is the role of calcium and vitamin D during pregnancy?
1. What dose and treatment regimens could be used to correct vitamin D deficiency in pregnancy?
For routine supplementation, current DoH guidance recommends 10mcg (400 units) daily in all pregnant women
(13); however, this will not correct deficiency in pregnancy where that has been identified. Consensus guidance on
doses adequate to correct vitamin D deficiency in pregnancy does not exist and hence there is a need to interrogate
the primary literature.
We identified a number of studies investigating vitamin D dosing in pregnant women and these are summarised in
the Appendix. (19;21-29) The majority of these studies were conducted in the second and third trimesters and as can
be seen from the table they varied in design; duration; doses and products of vitamin D used; latitude, ethnicity, and
sun exposure habits of participants; baseline maternal vitamin D levels and assay methods used to determine
25OHD. Differences in reported increases between one study (19) and the others with respect to rises in vitamin D
levels may be explained by variations in the studies.
As well as the range of outcomes reported varying between the studies, the range of doses investigated also varied
significantly. The highest daily dose studied in pregnancy was 4000units/daily starting from weeks 12 – 16 and
continuing to term (23) and the highest weekly dose was 35,000units/week, which was given between gestational
weeks 26-29.(27) Single bolus doses used in later pregnancy ranged from 60,000units to 600,000units. (2426;28;29) The cumulative doses to which patients were exposed also varied between a range of 60,000 – 1,200,000
units, given as 600,000 unit doses at the 7th and 8th months in one study (26), and with no adverse pregnancy
outcomes reported for this range.(19;21-29)
Using the evidence base to determine recommendations for dosing is not easy given the variability outlined above
and in the Appendix. The use of 1000units/day is too low a dose for correction of deficiency in pregnancy, particularly
given that 10-15 minutes of direct exposure to sunlight can release up to 20,000 units of vitamin D into the circulation
in Caucasians (though this time would be longer in people with pigmented skin). (6;15) Hence, many researchers
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have logically inferred that doses similar to those used in the general (vitamin D deficient) population (i.e. around
300,000 units cumulatively)(1) are more likely to correct deficiency in pregnant women than the lower doses used for
routine supplementation. The need for further research is widely acknowledged. (4;6;7;12;15;29).
2. When should vitamin D deficiency be corrected in pregnancy?
Most of the studies cited involved women in the second or third trimesters of pregnancy; the majority of skeletal
growth and development occurs during this period and hence treating particularly during this time is advisable. (8;14)
In addition, since the first trimester is more likely to be associated with teratogenicity, treating during this time may be
associated with greater theoretical risks. (30) A sensible overall dosing recommendation might, therefore, be a
300,000 unit cumulative dose given during the second and third trimesters of pregnancy. Whilst in the UK no specific
guidance exists in relation to how best to achieve this cumulative dose in pregnant vitamin D deficient women,
guidance does exist in other countries. (31-33) For example, the Swiss Federal Office of Public Health and the
American College of Obstetricians and Gynaecologists recommend a daily intake of 1000-2000 units with an upper
limit of 4000 units/day; (32) the Italian Society for Osteoporosis recommends similar dosing and avoidance of single
bolus doses >25,000 units;(31) and the French Society of Paediatrics recommends large single doses up to 80,000–
100,000 units, but only from the 7th month of pregnancy. (33)
In our view, from the evidence base we have been able to identify, reasonable recommendations in relation to dosing
for vitamin D deficiency in pregnancy might include:




Using a low dose of vitamin D (e.g. 400 units (10mcg) as suggested by the DoH for routine supplementation)
during the first trimester. (13) Consideration should be given to using corrective doses in the second and third
trimesters, when skeletal growth and development occurs (8), if these are deemed necessary.
Use of an oral corrective dose of 4000 units per day for up to 11 weeks to provide a cumulative dose of around
300,000units in the second or third trimester.
There is no consensus on what constitutes a very low vitamin D level, but a level of less than 15nmol/L, for
example, would be considered as being very low by many clinicians. If the baseline vitamin D level is very low
and the woman is in the second or third trimester of her pregnancy then slightly faster or even rapid correction
may be required particularly if there are unmodifiable risk factors. In these cases it would be rational to use
doses higher than 4000units/day, but not more than 10,000units/day (1;34) in the second or third trimesters.
E.g. a daily dose of 5000 units for 8–9 weeks or 7000 units for 6-7 weeks or 10,000 units for 4-5 weeks would
provide a similar cumulative dose of around 300,000 units. The rationale for using no more than 10,000
units/day is due to the theoretical possibility of toxicity (1) and malformations (34) in humans if very high doses
(i.e. >10,000 units/day) are used. However, it should be noted that this higher dose recommendation is not
supported by any studies, but rather is an upper physiological limit for which limited safety data in pregnancy do
not indicate a high possibility of harm. (34-37) Therefore we suggest that these higher doses should only be
used with the input of an obstetrician and with monitoring of calcium levels.
There is limited evidence to support the use of large single doses of vitamin D, such as 60,000 unit single doses
used in the second trimester by two groups of researchers. (24;28) Though vitamin D levels were elevated for a
time after dosing, they were not sustained throughout pregnancy and declined after 2-3 months. This means
that there would be a need to repeat these large single doses. This, in addition to theoretical safety concerns
about the use of large single doses of vitamin D mean that the daily dose regimens described above may offer a
more reliable and theoretically, safer option. Once deficiency has been addressed and treatment moves on to
maintenance, a dose consistent with that used in the general population is appropriate (i.e. 800units to
2000units/daily). (1)
In determining the regimen to use the following are useful factors to consider:




The severity of vitamin D deficiency (i.e. baseline vitamin D value) and the need for rapid correction.
Whether there are un-modifiable risk factors (such as vegetarian diet or covering of the skin for cultural reasons)
that may affect the ability to maintain vitamin D levels once deficiency is corrected.
The trimester of pregnancy. Treatment should ideally begin after the first trimester because of the lack of data
on its use in first trimester and also because the majority of skeletal growth and development is thought to occur
after the first trimester. In addition, if a woman is already in her third trimester when vitamin D deficiency is
identified, a higher dosing regimen over a shorter time period may be considered (e.g. up to 10,000units/day for
4-5 weeks to provide a cumulative dose of 300,000units).
Whether tolerability and compliance issues are likely. For example, a high dose vitamin D regimen may involve
taking a number of tablets to achieve the high dose and this could be problematic for some women.
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Medicines Q&As


Whether it is approaching summer or winter in the UK and/or whether any holidays in the sun are planned. In
such cases it would be prudent to avoid using high doses used for rapid correction (i.e. 10,000units/day).
Local availability of vitamin D products
3. Are there data to support the use of high dose regimens (i.e. up to 300 000 units cumulatively) during
pregnancy?
Safety data for high dose vitamin D regimens used during human pregnancy are limited.
Of the studies in Appendix 1 that reported neonatal outcomes, none reported any adverse pregnancy outcomes.
(19;23-27;29) The cumulative doses of vitamin D used by these studies were between 60,000 to 1,200,000 units
given either as daily doses of up to 4000 units, weekly doses of up to 35,000 units or single bolus doses of up to
600,000 units). (19;23-27;29) Other human safety data that report neonatal outcomes are limited to case reports,
usually relating to patients with concomitant conditions such as thyroid disease or patients who had taken a
particularly high dose inadvertently. (34-37) These data suggest that vitamin D, used at high doses (up to 250,000
units/day) was not associated with an increased risk of congenital malformation, although obviously, the data are
insufficient to confirm that there is unequivocally no risk. (34-37)
The limited safety data that report neonatal outcomes in human pregnancy, relate to use in the second or third
trimesters. (19;23-27;29;34-37) Use of high dose vitamin D in the first trimester should therefore be avoided as far as
possible, due to the lack of safety data. In theory, high doses of vitamin D could cause maternal hypervitaminosis D
and subsequently maternal, foetal and/or newborn hypercalcaemia. (34) Although it may also be true that the foetus
is relatively well protected from excessive maternal levels by homeostatic mechanisms, the theoretical risk of
maternal and foetal hypervitaminosis D or hypercalcaemia is a concern as it could lead to adverse pregnancy
outcomes. In animal studies where extremely high relative doses were given to pregnant mice, rats, pigs or rabbits,
facial and skeletal malformations, degradation of coronary smooth muscle, decreased rate of ossification of the
proximal phalanges and supravalvular aortic stenosis were reported. Although there was no statistical analysis of the
findings, a theoretical possibility of malformations in humans was raised if very high doses are used. (34) Therefore,
it is suggested that single high doses of vitamin D are avoided (i.e. >10,000 units/day). (1;15)
4. What available products would be best to use to correct vitamin D deficiency in pregnancy?
Vitamin D deficiency in pregnancy should be managed with colecalciferol or ergocalciferol; however, no licensed
high dose oral vitamin D products were available on the UK market at the time of writing (i.e. products giving
>800units per unit dose). There are licensed products that enable a dosing regimen of 4000units/day to be used and
do not contraindicate use in pregnancy (e.g. five x 800units capsules of Fultium D3® or tablets of Desunin®).(38;39)
Products containing vitamin A (such as Cod Liver Oil) should be avoided because this is a known teratogen. More
information on product selection is available from http://www.medicinesresources.nhs.uk/en/Communities/NHS/SPSE-and-SE-England/Medicines-Information/Discontinuation-Supply-Shortage-Memos/Vitamin-D-deficiency-andinsufficiency-available-products/
5. How often should a pregnant women being treated for vitamin D deficiency be monitored?
For non pregnant patients, the National Osteoporosis Society suggests that serum calcium should be checked a
month after completing the loading regimen in case subclinical primary hyperparathyroidism has been unmasked.
They state that routine monitoring of serum vitamin D levels is unnecessary (unless there are concerns about
compliance or malabsorption) and that steady-state levels for vitamin D are reached three months after treatment
begins.(1)
In pregnancy, maternal, foetal or neonatal hypercalcaemia is of particular concern as it is hypothesised to result in an
increased risk of adverse pregnancy outcomes. (34) Regular monitoring of serum calcium levels, as well as an
awareness of the signs and symptoms of hypercalcaemia will help to prevent toxicity and allow timely intervention to
be made if needed. (34) However, there is no consensus or guidance on exactly how often a pregnant woman being
treated for vitamin D deficiency, or her neonate, should be monitored.
Therefore we suggest that, for pregnant women being treated for vitamin D deficiency, it may be prudent to check
maternal calcium levels a month after starting the regimen and then three months after starting the treatment (when
steady state levels for vitamin D are likely to have been attained) as is suggested for the general population. (1) If the
pregnant woman is still taking the treatment dose of vitamin D thereafter, calcium levels could be checked again
three months later or sooner if there are concerns about toxicity. If calcium levels are raised, then the prescriber
should review the prescription for vitamin D or reduce the dose. In the general population, re-checking of vitamin D
levels is only suggested if there are concerns about malabsorption or compliance. (1) However, if there is a need to
check serum vitamin D levels in pregnant or non pregnant individuals, it stands to reason that this should be done 3
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Medicines Q&As
months after the last dose when steady state levels have been achieved. It might also be sensible to check neonatal
calcium and vitamin D levels at delivery.
6. What is the role of calcium and vitamin D during pregnancy?
Combined calcium and vitamin D products should not routinely be used to correct deficiency due to the risk of
hypercalcaemia; instead pregnant women should try to have an adequate calcium intake (700mg) through their
diet.(1;40) Calcium calculators (e.g. http://www.rheum.med.ed.ac.uk/calcium-calculator.php) are available to help
patients and clinicians determine whether dietary modification and/or supplementation should be used.
Limitations
 It is important to provide pregnant women and new mothers with advice on modifying their lifestyle to
improve their vitamin D status. This document has not focussed on this aspect.
 The potential differences in efficacy between vitamin D2 and D3 are not addressed in this document
Information on the management of vitamin D deficiency in the general population as well as a discussion
about risk factors and target levels is available from National Osteoporosis Society Guidance
 This Q&A does not make recommendations on specific vitamin D products for a number of reasons.
However, the reader is directed to NHS Evidence so that they can make a judgement on this.
 There are no current UK guidelines on treating vitamin D deficiency in pregnancy.
 This document does not provide information or guidance about the management of vitamin D deficiency in
women who are breast-feeding or for their breast-fed infants.
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Quality Assurance
Prepared by
Sheena Vithlani, Principal Medicines Information Pharmacist, London Medicines Information Service, Northwick Park
Hospital, Harrow.
Date Prepared
30th January-July 2013
Contact:
nwlh-tr.medinfo@nhs.net
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Medicines Q&As
Checked by
Alexandra Denby, Regional MI Manager, London Medicines Information Service, Northwick Park Hospital, Harrow.
Date of check
January 2014
Search strategy


Medline: 1950 to present: (exp COLECALCIFEROL/ or exp ERGOCALCIFEROLS/ or exp VITAMIN D/) and (PREGNANCY
OUTCOME/ or PREGNANCY/ or PREGNANT WOMEN/ or exp PREGNANCY TRIMESTERS/). Limit to: Humans and Female
and English Language.
EMBASE 1980 to present; (PREGNANCY/ or REPRODUCTION/ or MOTHER FETUS RELATIONSHIP/ or PREGNANT
WOMAN/ or FIRST TRIMESTER PREGNANCY/ or SECOND TRIMESTER PREGNANCY/ or THIRD TRIMESTER
PREGNANCY/ or TERATOGENICITY/) and (*ERGOCALCIFEROL/ or *COLECALCIFEROL/ or *VITAMIN D/; or VITAMIN D
DEFICIENCY/). Limit to: Human and English Language]
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7
Medicines Q&As
Appendix 1 Studies of vitamin D use during pregnancy
There are limitations to these studies, such as small patient groups, none provide data for use in first trimester, not all provide anthropomorphic
data for the newborns and exact treatment durations/cumulative doses
Dose and regimen
Average vitamin D levels
Other endpoint(s)/outcomes/major
Estimated
during pregnancy
limitations
25(OH)D (nmol/L)
cumulative
(week/month of
(values reported as mean
Values quoted as mean or median averages
vitamin D
gestation of dose)
or median)
Unless specified, values are quoted for
Study details
dose in
Oral dosing unless
intervention vs. placebo/control group at
pregnancy
specified
baseline (before vitamin D) and at delivery.
After
(maximum
Baseline
*route unclear from
(ns=not statistically significant vs.
(change)
iu vitamin D)
literature
placebo/control)
 The only significant difference was in
fontanelle size, which was greater in the
Vitamin D2
Brooke (1980) (19)
control group (p<0.05).
1000units/day (from
28,000 to
168
20.2
Randomised, double Hypocalcaemia occurred in 5 infants in the
week 28-32 to term). 56,000 to
(+150)
blind study. Women from
control group and none in the treatment group
N=59
Indian subcontinent living
(p<0.01).
in the UK (latitude 51.5o,
 Incidence of infants considered small for
all seasons). Mean
gestational age was 28.6% vs. 15.3% in
Matched placebo.
16
vitamin D values stated
control vs. treatment group (ns).
0
20.0
N=67
(-4)
 Cord blood vitamin D: 10.2nmol/l vs.
137.9nmol/l
 Only 58 women (73%) had their levels
rechecked at delivery. Vitamin D levels were
Datta (2002) (21)
Vitamin D
considered ‘normal’ at delivery for 60% of
Interventional programme
800unitswomen (35/58) using this regimen.
for women from Asia,
1600units/day for 6
Middle/ Far East and
Max
 Choice of dose depended on level at week 36.
months of
Africa living in Cardiff, UK
possible
14
28 (+14)
 There are many limitations to this study, such
pregnancy.
(latitude 51.4o). Mean
288,000
as lack of detail regarding how many women
Trimester at point of
levels stated. Study
were treated with each dose, when treatment
initiation not
period/season
was started, and the loss of 27% to follow-up.
documented. N=80
not documented.
 No neonatal outcome measures were
presented.
Delvin (1986) (22)
 Infant vitamin D and calcium levels (measured
Vitamin D3
Randomised study in
at 4 days) were significantly higher those born
1000units/day
(from
56,000
65
French Caucasian
to mothers who were treated with vitamin D
week 27-term).N=20
women living in Lyon,
Not noted
(45 vs. 17.5nmol/L, p<0.0005). Rate of infant
France (latitude 45.7o).
weight gain was similar.
Study period; December

No
neonatal outcome measures were
Control. N=20
0
33
to June. Mean values
presented.
stated.
 Neonatal vitamin D levels were 45.5nmol/L,
57nmol/L and 66nmol/L respectively in the
67,000 to
400units/day N=166
79 (+17)
400units/day, 2000units/day and
78,400*
4000units/day groups respectively (p<0.0001).
Sufficient vitamin D levels were seen in
Hollis (2011) (23)
39.7%, 58.2% and 78.6% of the neonates
Randomised, double2000units/day
336,000 to
respectively (p<0.0001).
98 (+36)
blind study in women of
N=167
392,000*
 There were no differences between the groups
Hispanic, African and
58-61
in terms of gestational age or birth weight, or
Caucasian descent living
level of care required for the newborn.
in the USA (latitude 32o).
39.4 (Black)
 Baseline levels of vitamin D (approximately
Study period covered all
59.3
60nmol/L) indicated that the women included
672,000 to
seasons. Treatment was
(Hispanic)
could not be considered vitamin D deficient.
784,000*
started from between
74.6
 There was a high correlation between vitamin
week 12-16 and
(Caucasian)
D levels one month prior to delivery and at
continued through to
4000units/day
111
delivery, and these values were used for the
*cumulative
term. Mean values
N=169
(+49)
92 women missing delivery values. Levels of
dose
stated.
≥ 80nmol/L were achieved by 52.3%, 79.5%
dependant
and 83.9% taking 400IU, 2000IU and 4000IU
on delivery
respectively (p<0.0001 for 2000IU and 4000IU
date
vs. 400 IU).
Kalra (2011) (24)
Prospective longitudinal
cohort. Indian women
living in North India
(latitude 26.8o). All were
treated with 1g elemental
calcium. Median values
stated. Study period
(season) not documented
Vitamin D3
60,000units as a stat
dose in the second
trimester N=48
Vitamin D3
120,000units as a
stat dose in the
second and third (28
weeks) trimesters
N=49
60,000
32
26 (-6)
120,000
32
59 (+27)
 Statistically significant differences in birth
weight (~0.3kg), birth length (0.85cm), head
circumference (0.85cm, all greater in the
treatment groups) and diameter of anterior
fontanelle (0.75cm smaller in the treatment
group) were seen between the treatment and
control groups at birth and persisted until 9
months of age.
 Single large doses increase vitamin D levels
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Medicines Q&As
Marya (1981) (27)
Interventional study in
Indian women living in
North India (latitude
28.8o). Season not
documented.
Mallet (1986) (25)
Randomised study in
French Caucasian
women living in the North
of France (latitude 49.4o).
Study period: winter.
Sahu (2009) (28)
Randomised study in
Indian women living in
North India (latitude
26.8o). Pooled results for
summer and winter All
women were given 1g
elemental calcium/day
and advised to get at
least 60mins sunexposure/day on face,
forearms and hands.
Median values stated.
Roth (27)
Randomised study in
women living in
Bangladesh (latitude 23o).
Mean values stated.Study
period; autumn. .
Yu (2009) (29)
Randomised, controlled
study in the UK (latitude
51.5o) with women from
mixed ethnicity (Indian
Asian, Middle Eastern,
Black, and Caucasian).
Women randomised
within each ethnic group.
Vitamin D deficiency was
seen in 47%, 64%, 58%
and 13% respectively.
Median vitamin D values
stated. Study period over
several seasons.
Not
reported
Control N=43
0
Vitamin D3
1200units/day (from
week 28-term).N=25
75,000
Vitamin D2
600,000 units as a
stat dose in months
7 and then 8. N=20
1,200,000
Control. N=75
0
Vitamin D3
1000units/day (from
week 28-term).N=21
90,000
Vitamin D2
200,000units as a
stat dose *(7th
month). N=27
200,000
26 (+16 vs.
control)
Control. N=29
0
9
Vitamin D3
120,000units as a
stat dose at 5th and
then the 7th month.
N=37 (group C)
Vitamin D3
60,000units as a stat
dose at 5th month.
N=35 (group B)
39
 Maternal and cord blood calcium levels higher
in treatment groups compared to control.
Statistically significant only for stat dose group
(primary outcome).
 Cord blood vitamin D levels not tested.
 Increased neonatal birth weight in both
treatment groups (2.89kg in daily dose group
and 3.14kg in stat dose group) compared to
control group (2.73kg) (p≤0.05).
Not tested
25 (+15 vs.
control)
Not noted
240,000
40
53 (+13)
60,000
33
31 (-2)
Control N=14 (group
A)
0
26
24 (-2)
35,000units/week
(26-29 weeks to
term). N=80
378,760
(range
35,000560,000)
134 (+90)
44
Placebo. N=80
0
Vitamin D2
800units/day (from
week 27-term).
N=60
72,000
26
Vitamin D
<25nmol.L:
45%
42 (+16)
Vitamin D
<25nmol.L:
13%
Vitamin D3
200,000units as a
stat dose at week
27. N=60
200,000
26
Vitamin D
<25nmol.L:
42%
34 (+9)
Vitamin D
<25nmol.L:
7%
25
27
(+2)Vitamin
D
<25nmol.L:
40%
Control. N=59
0
39 (-5)
Vitamin D
<25nmol.L:
50%
for around 2.5-3 months, hence the apparent
lack of effect in the 60,000unit group.
However, both doses appeared to have
positive effects on neonatal outcomes.
 Cord blood vitamin D levels similar across
active treatment groups.
 Cord blood levels of vitamin D at delivery were
greater in mothers who had been treated; 1518nmol/L vs. 5nmol/L.
 Infant birth weights were not significantly
different between groups.
 Treatment regimens were equally effective.
One case of delayed neonatal hypocalcaemia
was observed in the control group (on day 6).
 Mean daily sun exposure was 2.5 hours in the
summer and 4 hours in the winter.
 Target level of 80nmol/L achieved by 34% of
women in group C, 5.7% in group B and 7% in
group A.
 A single dose of 60,000 in the second
trimester was not able to significantly increase
the maternal vitamin D concentration at
delivery.
 Neither dose induced hypercalcaemia.
No neonatal outcome measures were
presented.
 Cord blood levels of vitamin D at delivery were
greater when mothers who had been treated;
103nmol/L vs. 39nmol/L.
 Vitamin D levels >50nmol/L were attained
by100% of mothers (97% of mothers had
levels ≥80nmol/L) and 95% of neonates in the
treatment group compared with 21% (6.3%)
and 19% respectively in the placebo group.
 There were no significant between-group
differences in birth weight, birth length or head
circumference.
 35,000 units/week did not induce
hypercalcaemia.
 Cord blood levels of vitamin D at delivery
were greater in the treatment groups
mothers; 26-27nmol/L vs. 17nmol/L.
 No differences in infant birth weights
between groups.
 Target level of 50nmol/L achieved by 30% of
women in the treatment groups at term and
only 8% of babies at birth. This suggests
that 800 units/day may be inadequate to
raise the levels sufficiently
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