Vitamin D3 and DHA play important roles in pregnancy. Vitamin D3 deficiency has been associated with increased risk of preeclampsia, gestational diabetes, low birth weight, preterm delivery, and impaired neonatal immunity. It is recommended that pregnant women take a daily supplement of 10 micrograms of vitamin D3. DHA is important for brain and eye development of the fetus. Ensuring adequate DHA through diet or supplements can help reduce risks of preterm birth and improve infant cognitive development and immune response. Supplementation with DHA during pregnancy and lactation has shown benefits.

1. WEBINAR POGI PALEMBANG 2020
Peran penting nutrisi dalam kehamilan – Minggu 13 Desember 2020 13.00-15.00 WIB
POGI PALEMBANG
PERAN VITAMIN D3 DAN DHA
DALAM KEHAMILAN
Abarham Martadiansyah
Divisi Kedokteran Fetomaternal KSM/Bagian Obstetri dan Ginekologi
RSUP dr. Mohammad Hosein/ Fakultas Kedokteran Universitas Sriwijaya Palembang
2020

2. NUTRISI DALAM KEHAMILAN
https://www.hopkinsmedicine.org/health/wellness-
and-prevention/nutrition-during-pregnancy
Recommends the following key components
of a healthy lifestyle during pregnancy:
•Appropriate weight gain
•A balanced diet
•Regular exercise
•Appropriate and timely vitamin and mineral
supplementation
The Academy of Nutrition and Dietetics
Ideal Foods to Eat During Pregnancy

3. NUTRISI DALAM KEHAMILAN
https://www.hopkinsmedicine.org/health/wellness-and-
prevention/nutrition-during-pregnancy
The following foods are beneficial to your health and fetal
development during pregnancy
• Vegetables and Fruits • Dairy
• Protein

4. PERAN VIT D3
DALAM KEHAMILAN

5. VITAMIN D3 DALAM KEHAMILAN
* Logan VF, Gray AR, Peddie MC, Harper MJ, Houghton LA. Long-term vitamin D3 supplementation is more
effective than vitamin D2 in maintaining serum 25-hydroxyvitamin D status over the winter months. Br J Nutr.
2013 Mar 28;109(6):1082-8. doi: 10.1017/S0007114512002851. Epub 2012 Jul 11.
• Vitamin D is a Secosteriod (steroid with a broken ring)
• The most important compounds in this group are vitamin
D3 (cholecalciferol) and vitamin D2 (ergocalciferol)
• Vitamin D2 and D3 are collectively called calciferol
• It is a pro hormone with its active form calcitriol
• Vitamin D3 is three times more effective and has a longer
half life than vitaminD2
Vitamin D

6. VITAMIN D3 DALAM KEHAMILAN
Source of Vitamin D
• Vitamin D subcutaneously produced in
humans from 7- dehydrocholecalciferol
upon exposure to ultraviolet light B
(UVB) radiation
• Fish-liver oils
• Fatty fish
• Mushrooms
• Egg yolks
• Liver

7. VITAMIN D3 DALAM KEHAMILAN
Metabolism of Vitamin D in Human Body

8. VITAMIN D3 DALAM KEHAMILAN
VITAMIN D METABOLISM IN PREGNANCY
Møller UK, Streym S, Mosekilde L, Heickendorff L, Flyvbjerg A. Frystyk J, et al. Changes in calcitropic hormones, bone markers and insulin-like growth
factor I (IGF-I) during pregnancy and postpartum: a controlled cohort study. Osteoporosis International 2013;24(4):1307-20
By 12 weeks of gestation, 1,25(OH)2D levels are more than twice that of a non
pregnant adult and continue to rise two to threefold from the nonpregnant baseline
rising to over 700 pmol/l
There is an increase in Vitamin D Binding Protein (VDBP) and Free 1,25(OH)2D
levels
Calcitonin rises during pregnancy and stimulates renal 1-α-hydroxylase gene
expression independent of calcium levels & also protects by opposing hypercalcemia

9. VITAMIN D3 DALAM KEHAMILAN
*food, nutrition board. institute of medicine. dietary reference intakes for calcium and vitamin d. washington dc: national academy press, 2010.
**dawson-hughes b. serum 25-hydroxyvitamin d and functional outcomes in the elderly. americanjournal ofclinical nutrition2008;88(2):527s-540s.
• Institute of Medicine defined adequate vitamin D status as
having serum 25-hydroxyvitamin D concentrations greater
than 50 nmol/L (or 20 ng/mL) in both the general population
and pregnant women.*
• Some studies have proposed that concentrations around 80
nmol/L (32 ng/mL) are optimal since they suppress PTH
levels and lead to the greatest calcium absorption.**
WHAT IS THE OPTIMUM VITAMIN D LEVEL?
An increased dietary intake is
required to maintain the
increase serum levels

10. VITAMIN D3 DALAM KEHAMILAN
RECOMMENDED INTAKE
Chief Medical Officers for the United Kingdom. Vitamin D -adviceonsupplementsforatrisk groups.Cardiff, Belfast, Edinburgh, London:
Welsh Government, Department of Health, Social Services and Public Safety, The Scottish Government, Department of Health; 2012
• The 2012 recommendation from UK Chief Medical Officers and NICE guidelines
state that all pregnant and breastfeeding women should take 10 micrograms of
vitamin D supplements daily
• 1 micrograms is 40 IU
• Three categories of vitamin D supplementation recommended are : General,
High risk (high risk for pre eclampsia & high risk for vitamin D deficiency),
and Deficient

11. VITAMIN D3 DALAM KEHAMILAN

12. VITAMIN D3 DALAM KEHAMILAN
SCREENING OF VITAMIN D DEFICIENCY
DURING PREGNANCY
Vitamin D in pregnancy, scientific impact paper no. 43, July 2014, Royal college of obstetricians and gynaecologists
• Routine screening of Vitamin D levels are not advisable
• Even screening in all high risks (like on the basis of skin colour or coverage,
obesity, risk of preeclampsia, or gastroenterological conditions limiting fat
absorption) is not cost effective
• Measurement of vitamin D levels is recommended only in a
hypocalcaemicor symptomatic woman

13. Why vitamin D is important
during pregnancy ?
VITAMIN D3 DALAM KEHAMILAN

14. VITAMIN D3 DALAM KEHAMILAN
Vitamin D deficiency during pregnancy is associated with
Preeclampsia
Insulin resistance &
gestational diabetes
mellitus
Immune modulation
Preterm delivery LBW
Impaired neonatal
immunity

15. VITAMIN D3 DALAM KEHAMILAN
Vitamin D and Preeclampsia
In a meta analysis of 8 studies
published in 2013, it was found
that Maternal vitamin D
deficiency in pregnancy
(25(OH)D < 50 nmol/L (20
ng/mL)) has been associated
with an increased risk of pre-
eclampsia

16. VITAMIN D3 DALAM KEHAMILAN
Vitamin D and Preeclampsia
In meta analysis of 3357 papers
published in 2013 in BMJ , it
was found that low levels of
Vitamin D is significantly
associated with new onset
hypertension and proteinuria in
pregnancy

17. VITAMIN D3 DALAM KEHAMILAN
Vitamin D and Preeclampsia
• Vitamin D is a potent endocrine suppressor role in renin
biosynthesis for the regulation of the renin-angiotensin
system
• Vitamin D deficiency cause excess activity in Th-1 type
cytokines and decrease immunological tolerance for
implantation and trigger preeclampsia
• Vitamin D has angiogenetic properties thus deficiency
associated with narrowing of spiral arteries leading to pre
eclampsia
Bakacak M, Serin S, Ercan O, et al. Comparison of Vitamin D levels in cases with preeclampsia, eclampsia and healthy pregnant
women. International Journal of Clinical and Experimental Medicine.2015;8(9):16280-16286.

18. VITAMIN D3 DALAM KEHAMILAN
Vitamin D in pregnancy, scientific impact paper no. 43, July 2014, Royal college of obstetricians and gynaecologists
• Women at high risk of pre-eclampsia are advised
to take at least 800 units a day combined with
calcium
Vitamin D and Preeclampsia
Recomendation

19. VITAMIN D3 DALAM KEHAMILAN
Vitamin D and Gestasional Diabetes
• Maternal serum 25-hydroxy
vitamin D(3) concentration in
GDM and IGT groups at 24-28
weeks of gestation were
significantly lower than non-
GDM controls

20. VITAMIN D3 DALAM KEHAMILAN
Vitamin D and Gestasional Diabetes
• Farrant et al studied 559
pregnant women in India and
found no association
between second trimester
25(OH)D levels and GDM

21. VITAMIN D3 DALAM KEHAMILAN
Vitamin D and Low Birth Weight
• Its was cross-sectional, descriptive analytical study involving 112 neonates in Iraq
• Mean maternal vitamin D (vit D) level was 31.46 nmol/L in the study
• Vitamin D levels were significantly lower in mothers of LBW

22. VITAMIN D3 DALAM KEHAMILAN
Vitamin D and Low Birth Weight
• Vitamin D during pregnancy is important for fetal
skeletal development, tooth enamel formation and
perhaps general fetal growth and development
• Approximately 25-30 g of calcium are transferred to the
fetal skeleton by the end of pregnancy, this requires
high levels of D3
• Mannion et al., in 2006 found that with every additional
40 IU of maternal vitamin D intake, there was an
associated 11-g increase in birth weight
Mannion C, Gray-Donald K, Koski K. Milk restriction and low maternal vitamin D intake during pregnancy are associated
with decreased birth weight. CMAJ. 2006;174(9):1273–1277.

23. VITAMIN D3 DALAM KEHAMILAN
Vitamin D and Preterm Delivery
• Maternal circulating 25-OHD deficiency
<50 nmol/L is associated with preterm
delivery
• Vitamin D supplementation suggested that
25-OHD serum concentration > 100 nmol/L
(vs <50 nmol/L) could significantly reduce
the risk ofPTB

24. VITAMIN D3 DALAM KEHAMILAN
Chesney RW.Vitamin D and The Magic Mountain: The anti-infectious raole of the vitamin. J Pediatr 2010; 56: 698– 703
Vitamin D and Preterm Delivery
• Protective effect is due to immunomodulator effects of
25-OHD
• Vitamin D might protect against PTB by reducing
infection and inflammation
• Inhibits inflammatory factors, such as tumour necrosis
factor-α and interleukin & promotes anti-
inflammatory cytokine and cathelicidin
• Improves placental function, and reduces oxidative
stress

25. VITAMIN D3 DALAM KEHAMILAN
Penatalaksanaan defisiensi vitamin D dalam kehamilan
• Treatment : either with cholecalciferol
20 000 IU a week or ergocalciferol 10 000 IU twice a week
• Duration : 4 – 6 weeks
• Maintenance dose:1000 IU daily throughout the pregnancy
Vitamin D: screening and supplementation during pregnancy, committee opinion number 495, july 2011 (reaffirmed 2017), The American
College of Obstetrician and Gynaecologists.
National Institute for Health and Clinical Excellence. Antenatal care.NICE clinical guideline 62. Manchester: NICE; 2008.

26. VITAMIN D3 DALAM KEHAMILAN
DRUG SAFETY DURING PREGNANCY
• US FDA pregnancy category :C
• US Recommended DA during pregnancy and lactationis 400 IU and
600 IU respectively
• Both RCOG and ACOG advocate routine 400 IU daily supplementation
of Vitamin D during pregnancy and lactation
• The daily upper safe limit for vitamin D has been set at 4000 IU by
IOM and 10,000 IU by the Endocrine Society
• Animal studies have shown foetal abnormalities associated with
hypervitaminosis D, similar to supravalvular aortic stenosis syndrome
National Institute for Health and Clinical Excellence. Antenatalcare.NICE clinical guideline 62. Manchester: NICE; 2008

27. PERAN DHA
DALAM KEHAMILAN

28. DHA DALAM KEHAMILAN
Linoleic Acid (LA)
Eicosapentanonic
Acid (EPA)
Docosahexaeonic
Acids (DHA)
Gamma-linolenic
Acid (GLA)
Arachidonic Acid
(AA)
converts to
converts to
converts to
converts to
Anti-inflammatory products
Pro-inflammatory products
desaturases
and
elongase
Alpha- linolenic Acid (ALA)
Omega – 6 Family Omega – 3 Family

29. DHA DALAM KEHAMILAN
Omega- 3fats are essential for
healthy brain and visual development
• Large proportion of the brain (60%) is made up of omega-3 fats
• DHA (docosahexanoic acid) is the main type of omega-3 fats in the brain andeyes
• 75% of brain cells are formed before birth and the other 25% are in place by age of 1
year

30. DHA DALAM KEHAMILAN
Important to directly consumepre-formed EPA and DHA
Linoleic Acid (LA)
Alpha- linolenic
Acid (ALA)
Omega – 6Family Omega – 3Family
Gamma-linolenic
Acid (GLA)
Arachidonic Acid
(AA)
converts to
converts to
converts to
converts to
Anti-inflammatory products
Pro-inflammatory products
desaturases
and
elongase
Flaxseed, chia seed,
walnuts, canola oil,
dark green vegetables
Fish oil, salmon, tuna,
fatty fish, mackerel
Fish oil, salmon, tuna,
fatty fish, algae oil
Soya bean, corn,
canola oil
Evening primrose
oil
Meat
Eicosapentanonic
Acid (EPA)
Docosahexaeonic
Acids (DHA)

31. DHA DALAM KEHAMILAN
Problem with relying only
on food sources
Image Source: http://mediconweb.com
▪ Mercury - neurotoxin
- Avoid swordfish, king mackerel,
shark, tilefish
▪ Eat 2 servings of oily fish per
week e.g. salmon, mackerel, tuna
- However, oily fish not as common
as white fish in Southeast Asia

32. DHA DALAM KEHAMILAN
Supplementing pregnant and lactating women –
Pregnancy Outcomes
• 4 meta-analyses and 2 large RCT consistently show protective effect of
omega-3 supplementation during pregnancy with reduction in the
incidence of early pre-term births
• Early preterm birth (before 34 weeks gestation) increases short and long
term morbidity and mortality
• Effect sizes range from 26% - 87.5%, with greater protective effects at
higher intake levels (600 -800 mg DHA/day)
• Most marked and significant reduction in high risk- pregnancies
• No adverse effects reported with higher dosages
Koletzko B et al Systematic Review and Practice Recommendations from an Early Nutrition Academy Workshop Ann Nutr Metab 2014:65:49-80

33. DHA DALAM KEHAMILAN
Supplementing pregnant and lactating women – Infant cognitiveand visual development
• Recent RCTs are mixed in methods of assessment
-> no conclusive evidence of benefits of omega-3 supplementation
• Breast-fed children had >> IQ points than non-
breast-fed
• Breastfed children performed similarly
irrespective of child genotype
• Formula fed GG children performed worse than
other children on formula milk (Steer et al,
2010)
In 5,934 children born in the UK 1990s and IQ
measured at 8 yrs

34. DHA DALAM KEHAMILAN
Supplementing pregnant and lactating women – Infant immune responseand allergies
Asthma outcomes
Klemens CM et al, 2011, BJOG
• Strong evidence of supplementation or 2 portions of oily fish/week resulting in
improved neonatal and maternal immune responses.
Long term effects
• Lower rates of allergic asthma at 19 years of
age (Olsen SF, 2008)
• Lower allergic sensitization of children
(Italy; Calvani M et al, 2006)
• Less doctor-diagnosed eczema
(Netherlands; Willers SM et al, 2006)
• Less atopic wheezing
(Mexico; Romieu I et al), 2007
Skin prick outcomes
Similar effects for high fish consumption

35. DHA DALAM KEHAMILAN
Allergies and the Immune Response
• Protective effects of omega-3 supplementation were seen if infants
received from 1-9 days of life until 12 months (Birch EE, 2010)
• Protective effects of fish intake if fish introduced prior to 9 months
of age ( Alm B, 2009).
• Strongest evidence in children with FADS genotype with low omega-3
synthesis.
Koletzko B et al Systematic Review and Practice Recommendations from an Early Nutrition Academy Workshop Ann Nutr Metab 2014:65:49-80
Supplementing infants born at full term

36. DHA DALAM KEHAMILAN
Koletzko B et al Systematic Review and Practice Recommendations from an Early Nutrition Academy Workshop Ann Nutr Metab 2014:65:49-80
Supplementing infants born at full term
Cognitive Development
• Results are mixed - limited by large degree of difference in dosages,
selected outcomes and methods of outcome assessment, no
adjustment for genetic variation in PUFA metabolism.
• Trend towards greater likelihood benefit with higher dosages
(DHA≥0.32% and AA ≥ 0.66%) and longer duration of higher postnatal
omega-3 supplementation (up to 1 year of age).
• Supplementation in early life may be better detectable at
later age in more specific tasks.

37. DHA DALAM KEHAMILAN
Pregnancy Lactation
Pre-
pregnancy
19
• Lower pre –term risk
• Better cognition and visual
development
• Improved immune responses and allergies
Infant Childhood
• Improved immune responses and allergies
Summary of evidence

38. DHA DALAM KEHAMILAN
Pregnant women
• Additional supply ≥200 mg DHA, to achieve ≥ 300 mg DHA/day
• Higher intakes (600 -800 mg) may provide greater protection against pre-
term birth
Breast-feeding women
Obtain ≥200 mg DHA/day to achieve human milk DHA content of 0.3%
fatty acids
Infant formula for term infants
• To provide 100 mg DHA/day and 140 mg AA/day.
• 2nd 6-months of life: continued supply of 100 mg DHA/day.
Very-low-birth weight infants
• 18-60 mg/kg/day DHA and 18-45 mg/kg/dayAA.
Koletzko B et al Systematic Review and Practice Recommendations from an Early Nutrition Academy Workshop Ann Nutr Metab 2014:65:49-80
Recommended levels

39. DHA DALAM KEHAMILAN
Undernutrition
• When total energy in low, essential
fatty acids are preferentially used
for energy expenditure.
• Micronutrient deficiencies of Fe
and Zn limit conversion rate of
essential fatty acids.
➔ Deficiency in EPA & DHA
Neufingerl N et al ( 2016) Intake of essential fatty acids in
Indonesian children: a secondary analysis of data from a nationally
representative survey, BJN
Intakes of essential fatty acids in Indonesia

40. DHA DALAM KEHAMILAN

41. DHA DALAM KEHAMILAN
Omega-3 fatty acids are important for infant health outcomes (pre-term,
neurodevelopment and allergy risk).
Pre-formed EPA and, in particular DHA are recommended due to low
conversion rates and genetic variation.
Regular supply prior to pregnancy is beneficial as it contributes to
accumulation of body stores
Recommend to consume 2 servings of oily fish as they also contain
other nutrients
Supplementation needed to meet higher requirements during pregnancy
and if oily fish intake is inadequate

42. TERIMA KASIH