Vitamin D deficiency has long been associated with poor bone development and has been identified as the cause of rickets. Although the incidence of rickets has declined with the current daily recommendations of vitamin D intake, the prevalence and additional consequences of low serum vitamin D levels have not been recognized until recently.1,2 The measurement of serum vitamin D in pregnancy has helped researchers establish the prevalence of vitamin D deficiency and elucidate adverse maternal and fetal outcomes associated with it.3 Prevention of these diseases and reduction of the risk for childhood illnesses that are linked to early vitamin D deficiency are possible with greater understanding of vitamin D physiologic components, risk factors for vitamin D deficiency, and methods of supplementation to attain optimal levels in pregnant and lactating women Vitamin D is a prohormone that is derived from cholesterol. The nutritional forms of vitamin D include D3 (cholecalciferol), which is generated in the skin of humans and animals, and vitamin D2 (ergocalciferol), which is derived from plants; both forms can be absorbed in the gut and used by humans. Controversy exists as to whether D2 or D3 is more effective in maintaining circulating levels of vitamin D in nonpregnant individuals, and specific data during pregnancy is unknown.4,5 In this review when we refer to vitamin D, we imply either vitamin D2 or D3. Vitamin D occurs naturally in fish and some plants but is not found in significant amounts in meat, poultry, dairy products (without fortification), or the most commonly eaten fruits and vegetables. The Food and Nutrition Board’s current recommendation for adequate intake of vitamin D is 200 IU/d for both pregnant and nonpregnant individuals aged 0–50 years.6 Wild salmon (3.5 oz) provides 600–1000 IU; farmed salmon has approximately 25% of this amount per serving.7 The same amount of mackerel, sardines, or tuna fish provides 200–300 IU. Cod liver oil (1 tsp) provides 600–1000 IU. One of the few plant sources of vitamin D is shiitake mushrooms, which provide 1600 IU.

1. ROLE OF VITAMIN D IN PREGNANCY &
LACTATION
DR ALKA MUKHERJEE
DR APURVA MUKHERJEE
NAGPUR M.S. INDIA

2. DR ALKA MUKHERJEE
MBBS DGO FICOG FICMCH PGDCR PGDMLS MA(PSY)
Director & Consultant At Mukherjee Multispecialty Hospital
MMC ACCREDITATED SPEAKER
MMC OBSERVER MMC MAO – 01017 / 2016
Present Position
 Director of Mukherjee Multispecialty Hospital
 Hon.Secretary INTERNATIONAL COUNCIL FOR HUMAN RIGHTS
 Hon.Secretary NARCHI NAGPUR CHAPTER (2018-2020)
 Hon.Secretary AMWN (2018-2021)
 Hon.Secretary ISOPARB (2019-2021)
 Life member, IMA, NOGS, NARCHI, AMWN & Menopause
Society, India, Indian medico-legal & ethics association(IMLEA),
ISOPRB, HUMAN RIGHTS
 Founder Member of South Rapid Action Group, Nagpur.
 On Board of Super Specialty, GMC, IGGMC, AIIMS Nagpur,
NKPSIMS, ESIS and Treasury, Nagpur for “ WOMEN SEXUAL
HARASSMENT COMMITTEE.”
mukherjeehospital@yahoo.com
www.mukherjeehospital.com
https://www.facebook.com/
Mukherjee Multispeciality
https://www.instagram.com/
Achievement
 Winner of NOGS GOLD MEDAL – 2017-18
 Winner of BEST COUPLE AWARD in Social
Work - 2014
 APPRECIATION Award IMA - MS
 Past Position
 Organizing joint secretary ENDO-GYN
2019
 Vice President IMA Nagpur (2017-2018)
Vice President of NOGS(2016-2017)
Organizing joint secretary ENDO-GYN
Organizing secretary AMWICON – 2019

3. OBSTETRIC ENDOCRINOLOGY
OPPORTUNITY, CHALLENGES AND CAUTION
• Opportunity, because the antenatal period presents a window during which
endocrine and metabolic manipulation can impact not only maternal and
fetal health, but also long-term outcomes in offspring.
• Caution is necessary, too, because the same therapy may lead to unwanted
adverse effects in the innocent fetus, and have (as yet unknown) long-term
complications.
• Challenges in obstetric endocrinology - unique - ethical and practical issues
make it difficult to conduct randomized placebo controlled trials as many
situations.
• The rapidly increasing incidence of endocrine dysfunction in obstetrics, and
the public health importance - require closer attention and debate.

4. • Vitamin D is – Fat soluble vitamin
• A key modulator of calcium metabolism in children and adults.
• Because calcium demands increase in the third trimester of
pregnancy, vitamin D status becomes crucial for maternal health,
fetal skeletal growth, and optimal maternal and fetal outcomes.
• Vitamin D deficiency is common
1. Pregnant women (5-50%) and in
2. Breastfed infants (10-56%), despite the widespread use of prenatal
vitamins, because these are inadequate to maintain normal vitamin
D levels (>or=32 ng/mL).

5. Two forms of vitamin D.
 Vitamin D3 (cholecalciferol) is produced from the conversion
of
7-dehydrocholesterol in skin and
 vitamin D2 (ergocalciferol) is produced in mushrooms and
yeast.
• The biologically active form of vitamin D is 1,25(OH)2D -
hydroxylation of vitamin D in the liver to 25(OH)D (25-
hydroxyvitamin D), which then undergoes renal hydroxylation
to form 1,25(OH)2D.
• D. Serum 25(OH)D concentrations reflect nutritional status.
• Production of 1,25(OH)2D in the kidney is tightly regulated by
plasma parathyroid hormone (PTH) as well as serum calcium
and phosphate levels.

6. • The interaction of 1,25(OH)2D with nuclear vitamin D receptors
influences gene transcription. Nuclear receptors for 1,25(OH)2D
are present - bone, intestine, kidney, lung, muscle and skin
Major sites of action include intestine, bone, parathyroid, liver
and pancreatic beta cells
• Vitamin D is a fat-soluble vitamin obtained largely from
consuming fortified milk or juice, fish oils, and dietary
supplements.
• It also is produced endogenously in the skin with exposure to
sunlight.
• Vitamin D that is ingested or produced in the skin must undergo
hydroxylation in the liver to 25-hydroxyvitamin D (25-OH-D),
then further hydroxylation primarily in the kidney to the
physiologically active 1,25-dihydroxyvitamin D.

7. • This active form is essential to promote absorption of calcium
from the gut and enables normal bone mineralization and
growth.
• During pregnancy, severe maternal vitamin D deficiency has
been associated with biochemical evidence of disordered
skeletal homeostasis, congenital rickets, and fractures in the
newborn
• Newborn vitamin D levels are largely dependent on maternal
vitamin D status & infants of mothers with or at high risk of
vitamin D deficiency are also at risk of vitamin D deficiency

8. Vitamin D and calcium metabolism in pregnancy
• During pregnancy and lactation, significant changes in
maternal vitamin D and calcium metabolism occur to provide
the calcium that is needed for fetal bone mineral accretion.
• During the first trimester, the fetus accumulates 2–3 mg/d in
the skeleton - this rate of accumulation doubles in the last
trimester.
• The body of a pregnant woman adapts to fetal requirements
by increasing calcium absorption in early pregnancy, with
maximal absorption in the last trimester.
• Along with the transfer of calcium to the fetus, the increased
intestinal absorption is balanced by enhancing urinary calcium
excretion, thereby keeping serum ionized calcium stable
throughout pregnancy.

9. • The fetal skeleton contains 30 g of calcium, most of which is
deposited during the third trimester of pregnancy.
• Lactation is a time of relative estrogen deficiency because of
elevated prolactin levels that suppress the release of
gonadotropins and, in turn, estrogen and perhaps stimulate
the release of PTHrP.
• Estrogen deficiency leads to bone resorption and
suppression of PTH levels. PTHrP levels are elevated and act
as a surrogate for PTH, thereby allowing continued
absorption of calcium from the urine and bone resorbption.

10. Factors that contribute to vitamin D deficiency
• Historically, most people relied on sun exposure to produce vitamin D.
• Due to modern indoor living and increased knowledge of the risks of skin
cancers - limited sun exposure - limit vitamin D production.
• Factors that contribute to vitamin D deficiency during pregnancy are
mainly due to
i. lack of direct sun exposure (for various reasons),
ii. lack of vitamin D in the diet (without supplementation), or
iii. genetic factors that limit the amount of vitamin D produced by the body.
• Some major factors - limited sun exposure due to indoor working
environments, sunscreen use, dietary choices, inadequate vitamin D3
supplementation, geographical location, time of year, darker skin
pigmentation, etc.

11. VITAMIN D DEFICIENCY IN PREGNANCY
• Vitamin D deficiency and insufficiency common across the
globe with high prevalence in women - antenatal and
lactating mothers
• Vitamin D requirements are probably greater in pregnancy -
physiologically higher 1,25-dehydroxy vitamin D levels in the
second and third trimesters – though levels do not correlate
directly with 25 hydroxy vitamin D concentrations -
a) the physiological rise in the active metabolite,
b) the enhanced intestinal calcium absorption, and
c) enhanced fetal requirement of calcium (250 mg/day in the
third trimester) all signifies the importance of vitamin D
biology in pregnancy

12. VITAMIN D DEFICIENCY & EFFECT ON CALCIUM
BALANCE & BONE METABOLISM
 Vitamin D and its active metabolite 1,25-dihydroxyvitamin D
(1,25(OH)2D) classical actions on calcium balance and bone
metabolism.
 Insufficient 1,25(OH)2D – inadequate absorption of calcium &
phosphate from the intestine - secondary hyperparathyroidism and a
lack of new bone mineralization (rickets in children and osteomalacia
in adults).
 Rickets is a childhood vitamin D insufficiency and usually develops
many months after delivery. However, the neonate is at risk of
hypocalcaemic tetany consequent on maternal hypovitaminosis D.

14. a. Poor & low birthweight,
b. neonatal hypocalcemia,
c. poor postnatal growth,
d. bone fragility, and
e. increased incidence of autoimmune diseases have been
linked to low vitamin D levels during pregnancy and infancy.
Adverse health outcomes of deficiency of vitamin D

15. • Vitamin D has an increasingly
recognized repertoire of non -
classical actions –
1. Promoting insulin action and
secretion,
2. Immune modulation and
3. Lung development. It
therefore has the potential to
influence many factors in the
developing fetus.
The three main steps in vitamin D
metabolism, 25-hydroxylation, 1α-
hydroxylation, and 24-hydroxylation are
all performed by cytochrome P450 mixed-
function oxidases (CYPs). These enzymes
are located either in the endoplasmic
reticulum (ER) (e.g., CYP2R1) or in the
mitochondria (e.g., CYP27A1, CYP27B1,
and CYP24A1).

16. DUAL ADVANTAGE
• A prohormone.
• A unique aspect of
vitamin D as a nutrient is
that it can be synthesized
by the human body
through the action of
sunlight.
• These dual sources of
vitamin D make it
challenging to develop
dietary reference intake
values.

17. • Calcium levels are normal in utero when maternal vitamin D
is insufficient.
• However, when maternal calcium delivery is interrupted at
birth, the neonate may develop hypocalcaemia.
• While the developing fetus requires approximately 30 g of
calcium, the maternal gut adapts and can overcome some
vitamin D insufficiency with increased calcium transport.

18.  Calcium homeostasis controls serum
calcium levels within a narrow range,
enhances calcium absorption from intestine
 The vitamin D endocrine system controls
whole body calcium homeostasis,
facilitates calcium in the kidneys
 Habitual dietary calcium intake and
physiologic states control vitamin D
metabolism.
 Increases bone calcification &
mineralization
 In excess, mobilizes bone calcium &
phosphates
 Vitamin D also regulates urinary calcium
excretion and bone metabolism.
Molecular and Cellular Endocrinology
Volume 453, 15 September 2017, Pages 36-45
What is the role of
vitamin D in calcium
homeostasis?

20. NORMAL VITAMIN D LEVELS IN PREGNANCY
• There is little consensus on what constitutes a ‘normal’
25(OH)D level in pregnancy.
• The Institute of Medicine - 20 ng/ml in pregnancy,
• Endocrine Society - 30 ng/ml or more
• However, using mathematical models, Holles et al. suggest
that pregnant women should have a circulating vitamin D >40
ng/ml, irrespective of how it is achieved
Am J Obstet Gynecol. 2010 May; 202(5): 429.e1–429.e9.
The recommended target range for non-pregnant adults is 32–
100 ng/mL (80–250 nmol/L), which appears to be a safe range
during pregnancy. In the United States, the current
recommendation for vitamin D intake during pregnancy is 200–
400 IU/d.

21. SYMPTOMS OF VITAMIN D DEFICIENCY
• Vitamin D deficiency is often asymptomatic.
• severe or prolonged deficiency may cause the following symptoms:
• Bone discomfort or pain in the lower back, pelvis, or lower
extremities
• Falls and impaired physical function
• Muscle aches
• Proximal muscle weakness
•Symmetric low back pain (in women)
Prior history of PIH, GDM, SMALL Size baby, previous baby having
Any musculoskeletal problem or rickets etc
Obese women

22. • The largest source of vitamin D in adults is synthesis from solar radiation;
half an hour of sunlight delivers 50 000 iu of vitamin D with white-
complexioned skin. Melanin absorbs ultraviolet B (UVB) from sunlight and
diminishes cholecalciferol production by at least 90%
• Dietary intake of vitamin D makes a relatively small contribution to overall
vitamin D status as there is little vitamin D that occurs naturally in the food
supply
What are the sources
of Vitamin D?

23. • Regular sun exposure is the most natural way
to get enough vitamin D. To maintain healthy
blood levels, aim to get 10–30 minutes of
midday sunlight, several times per week.
People with darker skin may need a little
more than this. Your exposure time
should depend on how sensitive your skin is
to sunlight.
What should be the duration & time to be spent
under Sun?

24. No exact time can be calculated, it is highly
dependent on many factors
• As a general rule, the higher the sun is in the sky (solar zenith
angle), the more vitamin D is made in the skin. By controlling
for solar zenith angle, as you wisely did, you also controlled
for factors such as latitude, season and time of day. However,
multiple other factors are at play, such as:
• Altitude, cloud cover, skin pigmentation, baseline 25(OH)D,
clothes worn
• Depth of the ozone column, oil and water content of skin,
reflective surfaces around you (albedo), amount of vitamin D
precursors in the skin
• Presence or absence of common “mutations” called single
nucleotide polymorphism (snps) of the vitamin D metabolic
machinery.

25. What is the Recommended amounts of vitamin
D during pregnancy? How much to be
supplemented in Indian pregnant women?

26. Recommended amounts of vitamin D
• Taking enough vitamin D during pregnancy is very important.
• Higher vitamin D intakes appear more effective and remain safe.
• Vitamin d recommendations
• Pregnancy And Lactation Organization
• 1500-2000 IU (38-50 Mcg) Endocrine Society
• 600 IU (15 Mcg) FDA
• 600 IU (15 Mcg) Institute Of Medicine
• *For women ages 19-50 years; **for lactation 4000-6000 iu/day is mother’s required intake if infant is not receiving 400
iu/day.
• an endocrine society clinical practice guideline https://www.Ncbi.Nlm.Nih.Gov/pubmed/21646368].
• Indian J Endocrinol Metab. 2014 Sep-Oct; 18(5): 593–596.
• doi: 10.4103/2230-8210.139204
• PMCID: PMC4171878
• PMID: 25285272
• Vitamin D supplementation in pregnancy

27. • Symptomatic or documented vitamin D deficiency in
pregnant women should be treated in the same manner as
in non-pregnant individuals.
• Daily doses of 4000 units/day are recommended for
treatment in pregnancy.
• The use of lower doses of vitamin D, as contained in most
prenatal calcium preparations (100-800 IU) cannot be
condoned in symptomatic patients, or in those with
documented low levels.
• In healthy, asymptomatic antenatal women, 1000-2000 IU
can be supplemented daily in the second and third
trimesters, without fear of vitamin D toxicity or
teratogenicity.

28. What are the risk factors for vitamin d
deficiency in pregnancy?

29. GENERAL RISK FACTORS FOR VITAMIN D DEFICIENCY
Factors
Northern latitudes, especially winter or spring
Limited sun exposure
Regular use of sunscreens
African American or dark skin
Obesity
Extensive clothing cover
Aging
Malabsorptive syndromes (cystic fibrosis, cholestatic liver
disease, inflammatory bowel disease, short gut syndrome)

30. Risk factors for vitamin D deficiency in
mothers
• Low socioeconomic status,
• Low educational status and
• Covered clothing style
• Obesity
• Reduced vitamin D concentrations are found in obese subjects.
• Pre-pregnancy obesity has been associated with lower levels of
vitamin D in both pregnant women and their neonates
J Clin Res Pediatr Endocrinol. 2018 Mar; 10(1): 44–50.
Published online 2018 Feb 26. doi: 10.4274/jcrpe.4706

31. What are the stages of vitamin D
deficiency and maternal & neonatal
adverse effects?

32. Stage
Serum 25(OH)D,
ng/mL Maternal adverse effects
Newborn infant adverse
effects
Severe
deficiency
<10 Increased risk of
preeclampsia, calcium
malabsorption, bone
loss, poor weight gain,
myopathy, higher
parathyroid hormone
levels
Small for gestational age,
neonatal hypocalcemia,
hypocalcemic seizures,
infantile heart failure,
enamel defects, large
fontanelle, congenital
rickets, rickets of infancy if
breastfed
Insufficiency 11–32 Bone loss, subclinical
myopathy
Neonatal hypocalcemia,
reduced bone mineral
density, rickets of infancy if
breastfed
Adequacy 32–100 Adequate calcium
balance, parathyroid
hormone levels
None, unless exclusively
breastfed
Toxicity >100 Hypercalcemia,
increased urine calcium
loss
Infantile idiopathic
hypercalcemia
Stages of vitamin D deficiency and adverse effects
Ann Nutr Metab 2018;72:179–192

33. The musculoskeletal manifestations of vitamin
D deficiency
Rickets and osteomalacia
Myriad metabolic, nonskeletal associations of vitamin D
deficiency
 Metabolic syndrome
 Immunomodulatory,
 Anabolic,
 Anti-infective and
 Anti-tumoral potential of vitamin D.
 Maternal secondary hyperparathyroidism
 Osteomalacia,
 Neonatal hypocalcemia and tetany,
 Delayed ossification of the cranial vertex,
 Enlarged size of cranial, fontanelles,
 Impaired fetal bone ossification

34. Low vitamin D and adverse maternal outcomes
in pregnancy
a. Induced hypertension,
b. High blood pressure in diabetic pregnancy,
c. Gestational diabetes mellitus,
d. Recurrent pregnancy loss
e. Preterm delivery
f. Primary caesarian section
g. Postpartum depression

35. Maternal effects of vitamin D deficiency
Preeclampsia and hypertensive disorders -3–10%
1. Women with preeclampsia - lower urinary calcium excretion,
lower ionized calcium levels, higher PTH levels, and lower
1,25 (OH)2 D levels
2. Low plasma calcium levels - several common mechanisms
associated with hypertension - increasing renal renin and PTH
levels.
3. Placental defects that cause decreased synthesis of active
vitamin D - key event in the development of this disease by
contributing to decreased calcium levels.
Int J Clin Exp Med. 2015; 8(9): 16280–16286.
The probable patho-physiology of Preeclampsia and
hypertensive disorders in vitamin D deficient state

36. Vitamin D’s prenatal benefits for mothers:
Vitamin D and Preeclampsia
• Leading causes of maternal death
• Deficiency in vitamin D may increase the risk of this
complication.
• Yet despite this evidence, the American College of
Obstetricians and Gynecologists has not found sufficient
evidence to advise supplemental vitamin D3 as a nutritional
intervention to prevent preeclampsia.

37. • Type 1 diabetes mellitus (type 1 DM)
• The Diabetes Autoimmunity Study in the Young reported that
autoantibodies to islet cells are correlated inversely with maternal dietary
vitamin D intake during pregnancy.
• More direct evidence of this correlation has come from the Europe and
Diabetes study in which vitamin D supplementation during the first year of
life decreased the risk of the development of type 1 DM (odds ratio, 0.67;
95% confidence interval, 0.5–0.8).
• In a Finnish study, children who received 2000 IU of vitamin D per day
during the first year of life had an 80% reduction in the risk of the
development of type 1 DM during a follow-up period of 30 years. In
contrast, children who were vitamin D-deficient or who were suspected to
have rickets at 1 year had a 2.4-fold increased risk of the development of
type 1 DM. The high doses of vitamin D that were used in this study clearly
establish the preventive effects of this vitamin in the development of type 1
DM.
Correlation between Vitamin D
and Gestational Diabetes

38. Vitamin D and Gestational Diabetes
• One recent study shows that blood sugar balance was more
easily achieved with sufficient blood levels of vitamin D.
• Another study reported that pregnant women who
supplemented with 50,000 IU of vitamin D3 once every three
weeks (about 2400 IU/day) significantly improved their
metabolic status, including fasting blood sugar levels, and
insulin levels.
Low blood vitamin D level could increase the risk of GDM, and
vitamin D supplementation during pregnancy could
ameliorate the condition of GDM.
https://pubmed.ncbi.nlm.nih.gov/29244241/#:~:text=Conclusions%3A
%20Low%20blood%20vitamin%20D,D%20supplementation%20amelio
rates%20GDM%20condition.

39. Link between Vitamin D and C-Section
1. Complications Preeclampsia & GDM iincrease the chances of C-Section
2. Research shows an indirect link between vitamin D and this alternative
delivery method.
3. One study showed that pregnant women with deficient vitamin D blood
levels were nearly twice as likely to deliver by this method compared to
pregnant women with higher vitamin D levels.
4. Other researchers reported that this was four times more likely.
5. Similarly, pregnant women who took 50,000 IU every three weeks
(average of about 2400 IU/day along with calcium), were three times less
likely to deliver via an alternative delivery method, compared to the
placebo group.
6. Low maternal vitamin D level was associated with increased risk of
primary C-section, uterine atony and postpartum hemorrhage.
Clin Gynecol Obstet. 2018;7(2):43-51doi: https://doi.org/10.14740/jcgo473w

40. Vitamin D’s prenatal benefits for infants:
Vitamin D and Preterm Birth
1. Leading causes of infant mortality, Vitamin D deficiency has
been linked to this pregnancy complication & study suggests
that sufficient levels of vitamin D may decrease the likelihood
by 40%.
2. It’s important to note that vitamin D and calcium
supplementation may play a role in this potential complication
Indian J Med Res. 2011 Mar; 133(3): 250–252.
Vitamin D sufficiency significantly
reduces the risk for preterm birth
increase in birth weight of baby and
improving the Apgar score at birth.
Role of vitamin D in reducing the risk of preterm labour
www.ijrcog.org › index.php › ijrcog › article ›

41. Vitamin D and Size at birth
• Low birth weight,
• birth length, and
• head circumference at birth – Deficiency of vitamin D
• Research shows that higher vitamin D levels are associated
with higher infant birth weight and larger head circumference.
• Further, vitamin D deficiency may be associated with low birth
weight, smaller head circumference, and decreased birth
length

42. Vitamin D benefits beyond pregnancy
• Maternal vitamin D status during pregnancy has clear effects on
fetuses as well as on newborn infants, and even on the health of
the child later in life - supplementation during pregnancy is so
critical - clear associations between vitamin D and bone,
respiratory and blood sugar health.
• Insufficient amounts of vitamin D during pregnancy - a
reduction in bone mass in infants that can persist for at least
nine years after birth.
• Respiratory health in newborns to 3-year-olds have also been
linked to maternal vitamin D intake during pregnancy.
How does a maternal vitamin D levels impact the
long-term health of offspring?

43. Researchers reported that in a cohort of ~30,000 pregnant
women, children born to women with prenatal vitamin D levels
of <54 nmol/L (21.6 ng/mL) were twice as likely to have blood
sugar imbalance than children born to women with prenatal
vitamin D levels of >89 nmol/L (35.6 ng/mL).

44. • Childhood illness and gestational vitamin D deficiency
• Asthma
• Multiple biologic actions suggest a correlation between
vitamin D deficiency and the asthma epidemic.
• Vitamin D signaling pathways and receptor
polymorphisms may have effects on Th1-
Th2 imbalance, smooth muscle contraction, airway
inflammation, prostaglandin regulation, and airway
remodeling, all of which can impact asthma control.

45. • Clinical studies indicate an inverse association between
vitamin D intake during gestation and wheezing in their
children during the first years of life.
• Post-hoc analysis of serum samples of asthmatic children
from the Childhood Asthma Management Program study
showed that approximately 35% of patients had levels of
vitamin D <30 ng/mL and that these children had lower lung
function and greater risks for exacerbations than those with
levels >30 ng/mL.

47. Vitamin D deficiency during lactation
• In the first 6–8 weeks of postnatal life, the vitamin D status of
a neonate is dependent largely on vitamin D that is acquired
through placental transfer in utero. In most infants, vitamin D
stores acquired from the mother are depleted by
approximately 8 weeks of age.
• Thereafter, vitamin D is derived from diet, sunlight, and
supplementation. In general, formula-fed babies receive
adequate vitamin D because it is added to all formulas in
amounts of 400 IU of vitamin D per liter.

48. • But the exclusively breastfed are at higher risk for vitamin D
deficiency.Human milk contains a very low concentration of
vitamin D (approximately 20–60 IU/L), which represents 1.5–
3% of the maternal level which is not sufficient to maintain
an optimal vitamin D level in the baby if exposure to sunlight
is limited.
• Breast-fed infants from vitamin D– deficient mothers
occasionally manifest life-threatening conditions such as
hypocalcemic seizures and dilated cardiomyopathy

49. Should all pregnant women be screened
for vitamin D deficiency?
When do you suggest vitamin D test to
your patients?

50. Should all women be screened for vitamin D
deficiency?
• The Royal College of Obstetricians and Gynaecologists
recommends screening for very high-risk women - those
with symptoms, brittle bones, or those with chronic
illness who may not be able to absorb vitamins from the
intestines.
Routine screening of all pregnant women for vitamin D
deficiency is not recommended, according to new
guidelines issued by the American Congress of
Obstetricians and Gynecologists (ACOG)

52. Taking vitamin D and calcium
supplements together in pregnancy:
what does the evidence say?

53. Taking vitamin D and calcium supplements together in
pregnancy:
• These results warrant further research.
• Whilst there are potential harms of taking combined calcium
and vitamin D supplementation, the benefits for those
at risk of pre-eclampsia may outweigh these harms.
Vitamin D plus calcium supplementation during pregnancy
appears to reduce the risk of pre-eclampsia, while vitamin D
alone appears to reduce the risk of low birth weight and
preterm delivery. However, supplementation with vitamin D
plus calcium appears to increase the risk of preterm birth.
e-Library of Evidence for Nutrition Actions (eLENA)

54. What is your opinion about single dose &
daily dose of vitamin D in case of
deficiency state?

55. • Timing and dosing regimen are crucial for vitamin D
supplementation.
• Daily administration is supposed to be the most physiological
way to correct vitamin D deficiency, but a less frequent
administration is likely to improve patient compliance to the
treatment, and help obtain a greater mean vitamin D 25-
hydroxylation

56. VITAMIN D TOXICITY
• Excess vitamin D supplementation can lead to hypercalcemia,
but vitamin D toxicity is extremely rare.
• It generally occurs only after ingestion of large doses of
vitamin D (>10,000 IU/day) for prolonged periods in patients
with normal gut absorption or those ingesting excessive
amounts of calcium.
• Patients with vitamin D toxicity can present with clinical
symptoms of hypercalcemia, including nausea, dehydration,
and constipation, or symptoms of hypercalciuria such as
polyuria and kidney stones.

57. • The lowest reported 25(OH)D level associated with toxicity
in patients without primary hyperparathyroidism and with
normal renal function is 80 ng/ml.
• Most patients with vitamin D toxicity have levels greater
than 150 ng/ml.
• One dosing study reported that vitamin D supplementation
with 1,600 IU/day or 50,000 IU monthly was not associated
with any laboratory parameters of toxicity and even failed to
increase total 25(OH)D levels above 30 ng/mL in 19% of
participants.

58. What does the new Cochrane evidence add?
• An important new Cochrane review update (Palacios et al., 2019)
summarises the evidence base for Vitamin D supplementation in
pregnancy; it includes 30 research studies and over 3700 pregnant
women were included.
• Before this review, we knew that babies from mothers who lacked
vitamin D have poorer outcomes, but it had not been convincingly
demonstrated that supplementation improved outcomes for
those at risk.
• It showed that taking vitamin D supplements in pregnancy:
• Probably reduces the risk of getting pre-eclampsia and gestational
diabetes
• May reduce the risk of having a low-birthweight baby.
• May reduce the risk of severe bleeding after birth.
• May make no difference to the risk of preterm birth before 37
weeks

59. CONCLUSION
• As we mentioned initially, obstetric endocrinology is a field
marked by both opportunity and caution.
• With the available evidence regarding vitamin d
supplementation, and the conflicting interpretations of
whatever has been published, it becomes challenging to issue
evidence-based guidelines.
• However, the benefit of vitamin d supplementation in
pregnancy is potentially even greater than in the nonpregnant
state
• Prescribe lower doses to pregnant women than to their
nonpregnant peers, perhaps because of an unfounded fear of
side effects.

60. • Symptomatic or documented vitamin d deficiency in pregnant
women should be treated in the same manner as in non-
pregnant individuals. Daily doses of 4000 units/day are
recommended for treatment in pregnancy.
• The use of lower doses of vitamin D, as contained in most
prenatal calcium preparations (100-800 IU) cannot be
condoned in symptomatic patients, or in those with
documented low levels.
• In healthy, asymptomatic antenatal women, 1000-2000 IU can
be supplemented daily in the second and third trimesters,
without fear of vitamin D toxicity or teratogenicity. No safety
data, however, is available for the first trimester with this
dose, either.

61. • Serum alkaline phosphate, a surrogate marker of vitamin D
deficiency, cannot be used as such in pregnancy, because of
the placental secretion of this enzyme.
• 25 hydroxy vitamin D levels may be measured in each
trimester, if easily affordable. In routine practice, however,
this investigation is not necessary.
• In resource constrained settings, patients on vitamin D
therapy can be screened for hypercalcemia by checking for
calcium crystalluria.

62. Vitamin D in pregnancy Coronavirus update
All adults, including pregnant and breastfeeding women, need
10 micrograms of vitamin D each day and should consider
taking a supplement containing this amount between
September and March.