hyperhomocystenemia in pregnancy information to be uploaded.

1. INDGMP3212007

2. Overview
Hyperhomocysteinemia
Prevalence in pregnancy
Clinical outcomes in Pregnancy
Diagnostic Measures
Treatment with emphasis on empirical management
Role of vitamin B6, B9 and B12 in management
Clinical Evidence

3. Homocysteine
Naturally occurring sulphur containing amino acid
Results from the demethylation of the essential amino
acid methionine.
Normal serum levels: 5 to 15 micromol/litre
Hyperhomocysteinemia –

4. Etiology of Hyperhomocysteinemia
Vitamin Deficiencies :
Folate (B9)
Methyl Cobalamin (B12)
Pyridoxine (B6)
Genetic causes:
Defects (due to gene mutation )in Enzyme causing
metabolism of homocysteine ( Rare )
Current Drug Metabol 2007 Jan;8(1):17-31

5. Determinants of Plasma homocysteine
Genetic factors
Physiological factors
Lifestyle
Folate deficiency ↑ ↑
Vitamin B12 deficiency ↑ ↑
Clinical
Conditions
Vitamin B6 deficiency ↑
Pregnancy ↓
Renal failure ↑
Hypothyroidism ↑
Drugs

6. Homocysteine levels in vegetarian and non
vegetarian life style – Epidemiology in India
India predominantly
follows vegetarian food
habits
Higher levels of
homocysteine due to
Vitamin B12 deficiency
www.veganhealth.org as accessed on 28th April 2012 Homocysteine Levels

7. Homocysteine and Pregnancy
Homocysteine conc. decreased in pregnancy due to
Hemodilution
Raised GFR
Hormonal changes of pregnancy
Increased fetal uptake
Hague WM Best Practice & Research Clinical Obstetrics & Gynaecology 2003;17(3):459–469, 2003

8. Indian Study
2010
Hyperhomocysteinemia in Pregnancy
In an Indian maternal nutrition study, two thirds of
pregnant mothers had low levels of vitamin B12
Only an occasional mother had low folate concentration.
Vitamin B12 and folate play vital role in one carbon (1-C)
metabolism, crucial for fetal growth
This study showed that the plasma tHcy concentration at
34 weeks gestation was lower in those who received
vitamin B12 supplementation compared to those who
received only folic acid or no supplementation
Katre P et al. Vitamin B12 and folic acid supplementation and plasma total homocysteine concentrations in pregnant Indian women with low B12
and high folate status Asia Pac J Clin Nutr 2010;19 (3):335-343

9. Hyperhomocysteinemia is an independent causal factor
in pregnancy complications
……..Current Drug Metabol 2007 Jan;8(1):17-31

10. Clinical outcomes in Pregnancy
Approximately 2-fold to 3-fold increased risk for :
• Pregnancy-induced hypertension
• Abruptio placentae
• Intrauterine growth restriction
Cobalamine deficiency :
• HELLP syndrome
• Abruptio placentae
• Intrauterine growth restriction
• Intrauterine fetal death
Pyridoxal 5-phosphate deficiency
• Increased risk for pregnancy-induced hypertension 4-fold
Hyperhomocysteinemia, Pregnancy Complications and the Timing of Investigation
Re´gine P. Steegers-Theunissen,et al. VOL. 104, NO. 2, AUGUST 2004
The American College of Obstetricians and Gynecologists as accessed on 29 th April 2012

11. Other congenital defects
spontaneous
miscarriage recurrent abortion
NTDs
IUGR
Hyperhomocysteinemia
Pre-term labour
Intrauterine fetal death Pre-eclampsia
placental abruption
Hyperhomocysteinemia, Pregnancy Complications and the Timing of Investigation
Re´gine P. Steegers-Theunissen,et al. VOL. 104, NO. 2, AUGUST 2004
The American College of Obstetricians and Gynecologists as accessed on 29 th April 2012

12. Association of Hyperhomocysteinemia &
Pregnancy complications, adverse pregnancy outcome.
As evident by clinical studies………..

13. J Nutr. 2006 Jun;136(6 Suppl):1731S-1740S
Women with hyperhomocysteinemia have
increased risk of pregnancy complications
and adverse pregnancy outcome

14. BJOG. 2006 Dec;113(12):1412-8
Maternal hyperhomocysteinemia is a risk factor for
Congenital Heart Disease
Clin Chem Lab Med 2005; 43(10): 1052-7
Early abortion, pregnancy complications and poor
pregnancy outcomes have been linked to
hyperhomocysteinemia

15. American Journal of Perinatology. January 2006; 23(1):31-35
Hyperhomocysteinemia during pregnancy is a risk
factor for development of preeclampsia and its
complications
Eur J. of Obs & Gynae & Reprod Biol 2003
Numerous studies have demonstrated association
between increased levels of homocysteine and
spontaneous miscarriages, IUGR, preeclampsia
and fetal death

16. Pregnancy outcomes are multi-factorial
Sundrani D.P. et al. / Medical Hypotheses 77 (2011) 878–883

17. Hyperhomocysteinemia as risk factor
Pregnant women with hyperhomocysteinemia have a 7.7-fold
risk for preeclampsia
Hyperhomocysteinemia associated with recurrent pregnancy
loss
MHTFR mutation in 16% cases
López-Quesada E, Vilaseca MA, Lailla JM. Eur J Obstet Gynecol Reprod
Biol. 2003 May 1;108(1):45-9.

18. Diagnostic Measures
 When to Screen ?
Values in early pregnancy are more reliable
Second-trimester plasma homocysteine concentrations do not
predict the subsequent development of pregnancy-induced
hypertension, preeclampsia, and intrauterine growth
restriction
Hogg BB, Tamura T, Johnston KE, Dubard MB, Goldenberg RL. Am J Obstet Gynecol. 2000 Oct;183(4):805-9
Zeeman GG, Alexander JM, McIntire DD, Devaraj S, Leveno KJ. Am J Obstet Gynecol. 2003 Aug;189(2):574-6 as accessed
on 28th April 2012

19. Sample Collection
Overnight fasting must
Morning sample
EDTA bulb
To be centrifuged immediately
Or kept on wet ice till centrifugation

20. Treatment
Dietary modification
Folate supplementation[500-5000microgram/day]
 Vitamin B12 supplementation
particulary for indian population due to high prevalance of
vegeterian diet
Supplementation of pyridoxine[B6]
Sundrani D.P. et al. / Medical Hypotheses 77 (2011) 878–883
Hague WM Best Practice & Research Clinical Obstetrics & Gynaecology 2003;17(3):459–469, 2003

21. Role of vitamin B6, B9 and B12 in management
Methionine is an essential amino acid obtained from
protein in the diet
Some methionine is turned into homocysteine
The body turns much of this homocysteine back into
methionine with the help of vitamin B12
Low vitamin B6 status can also cause elevated
homocysteine in some people
www.brewboost.com as accessed on 1st May 2012

22. Role of vitamin B6, B9 and B12 in management
Demethylation
Methionine synthase
Cystathionine beta
synthase
Transsulfuration
Available at www.medscape.com as accessed on Aug 2012
MTHFR- methyl tetrahydrofolate reductase

23. FOLIC ACID
Important cofactor in the Remethylation of Homocysteine
Making of new cells and cell replicatio n
Folic acid-vitamin B supplementation significantly
reduce total Hcy levels
Low conc associated with risk of preterm delivery,
Low birth weight infants and IUGR
AJCN. 2000; 71: 1295S-1303S,
Am J Obstet Gynecol. 2004 Dec;191(6):1851-7.
Bostom et al, 2002

24. VITAMIN B12
A cofactor, Methionine Synthetase (MS) in methylation
Enzyme, catalyses the transfer of CH3 group from
MethylTetrahydrofolate Homocysteine
In Vit. B12 def, folate is trapped as unusable MTHF,
causing functional folate deficiency.
Thus plays a key role in the remethylation of
Homocysteine to Methionine.

25. VITAMIN B6
A cofactor, Pyridoxal Phosphate in methylation
Reduces the level of homocysteine by the process of
transulfuration to cysteine & hence related
pregnancy complications are reduced
Vitamin B6 levels of mothers at the onset of
pregnancy have a positive correlation with birth
weight of newborns
Effective in the treatment of nausea and vomiting of
pregnancy
Int J Vitam Nutr Res. 1978;48(4):341-7

26. Clinical Evidence

27. Folate, Vitamin B12 & B6 - effective & safe to
reduce homocysteine levels
The relationship between serum homocysteine (hcy)
levels and pregnancy complications was studied
Homocysteine lowering effects of folate, vitamin B12 and
Vitamin B6
332 pregnant women
They were given-
folate- 5 mg/day, vitamin B12- 1000 mcg/day for 6 weeks
and of vitamin B6- 1000 mcg/day
Quereshi S et al. JPMA 60:741; 2010

28. Folate, Vitamin B12 & B6 - effective & safe to
reduce homocysteine levels
Quereshi S et al. JPMA 60:741; 2010

29. Conclusion
Folate, Vitamin B12 & B6 supplementation is effective & safe to reduce
homocysteine levels
Quereshi S et al. JPMA 60:741; 2010

30. Conclusion
Vitamins (folate, B6, B12) play important role in metabolism
of homocysteine
Deficiency of vitamins (folate, B6, B12) is associated with
hyperhomocysteinemia
Hyperhomocysteinemia may be associated with some of the
complications in preganancy
Supplementation of Folic acid, B6 and B12 is effective and safe
in reducing homocysteine levels

31. Prophylaxis
Folic acid and vitamins B6 and B12 are necessary in metabolism
of Hcys; therefore they can be used for both treatment and
prophylaxis of hyperhomocysteinemia
Proper diet
Abstaining from tobacco or smoking
Optimal physical activity
http://www.czytelniamedyczna.pl/3431,prophylaxis-and-treatment-of-hyperhomocysteinemia.html

32. Top Three “Best Practices” to Improve Birth
Outcomes & Reduce High Risk Births (NGA, June
2004)
Improve access to medical care and health care
services
Encourage good nutrition and healthy lifestyles
Eating healthy foods
Taking folic acid (Methylating agents)
Reduce use of harmful substances
Available at http://www.nga.org/cms/home/nga-center-for-best-practices/ as accessed on Aug 2012

33. Summary
Hyperhomocysteinemia is independent causal factor
for pregnancy complications
Folic acid, methylcobalamin and pyridoxine
deficiencies lead to hyperhomocysteinemia and are
prevalent in pregnant women
Supplementation of folic acid, methylcobalamin and
pyridoxine helps in management of
hyperhomocysteinemia