1. Outcomes of Pregnancy in Women with TPO Positive Status after Appropriate Dose Adjustments of Thyroxin-A Prospective Cohort Study.
Milann- The Fertility Center , Bangalore;India
Revathi S.Rajan
Pratibha Malik
Nupur Garg
Smitha Avula
Kamini A.Rao

2. INTRODUCTION RELEVANCE
Fetal thyroid function -> starts at 12 weeks.
Complete dependence -> maternal thyroid .
Thyroid hormone - essential for normal placentation.
Preterm delivery and vascular diseases like preeclampsia - faulty early placentation.

3. Subclinical Hypothyroidism
Potentially increased obstetric risks .
Prudent to start appropriate supplementation with L-Thyroxin.
Trimester specific reference ranges should guide supplementation.
First Trimester-0.1 to 2.5 m IU/L, Second Trimester-0.2 to 3 mIU /L and Third Trimester-0.3 t0 3 mIU/L.

4. TPO antibody Increased risk of obstetric complications
Greater risk of PE,FGR and low first minute Apgar scores [ PE and FGR - additive effect of thyroid dysfuction]
Increased risk of mid trimester abortion[Recent study]
Warrants close maternal and fetal surveillance.

5. AIMS AND OBJECTIVES PRIMARY;
To analyse the maternal and perinatal outcomes of TPO positive pregnant women after appropriate dose adjustments of L-Thyroxin.
SECONDARY;
A] To establish the prevalence of TPO antibody positivity in pregnant mothers with subclinical hypothyroidism.

6. B]To establish its associations with other co-morbidities like Antinuclear antibody [ANA] positivity.other autoimmune disorders and thrombophilias[APLA and Hyperhomocysteinemia]

7. MATERIAL AND METHODS
Prospective observational single group clinical study.
Conducted at Milann –The Fertility Center, Bangalore ;India between August 2013 and October 2014
An Informed Consent -obtained prior to the study.
Inclusion criteria- 1] Pregnant women with a booking TSH of >2.5 mIU /L .
2]Hypothyroid pregnant women[diagnosed prior to conception]

8. Exclusion criteria- Pregnant women whose TSH levels were less than 2
Exclusion criteria- Pregnant women whose TSH levels were less than 2.5mIU booking.
A positive TPO antibody level was > or = 35 IU/ml.
Strategy for surveillance:[as per TSH&f T4 levels]
-TPO pos hypothyroid women-Monitored every 3-4 weeks,dose adjustments[1-2 microgram /kbw]
-TPO neg- Monitored every 4-6 weeks for dose adjustments.

9. RESULTS

12. DISCUSSION 240/460 pts[52%] were hypothyroid.
143/460 pts[31.08%]were subclinically hypothyroid.
97/460 pts [21.08%] were of the overt gp.
115/240 pts [47%] were TPO positive
Background-Several studies have established the association of TPO positivity with adverse obstetric outcomes.
1]Higher risk of abortion and prematurity-Gafoor et al[2006.
2]TPO positivity in the first trimester was a risk factor for perinatal death and not thyroid hormone status-Mannisto T et al[2009].
3]Lesser obstetric complications in the L-thyroxin treated TPO positive gp compared to the untreated gp-Negro et al[2006]
4]Significant increase in past gestational htn,late abortions and fetal death in Tunisian women-Feki et al[2008]
5]3 fold increase in the risk of placental abruption-Casey and Abbassi et al[2005,2010]

13. Our study 21% of TPO pos pts-Threatened abortion
[4.3% had a missed abortion]
14.8% of these patients had gestational HTN .[3.5% had FGR]
60% of these pts had GGI/GDM.

14. Essential inferences
Significant associations - TPO positive pregnant women aged 30 yrs and above with Hhcy[p=0.017], APLA[ p=0.029] and BOH/RPL[p=0.067].
Those with antibody levels >600IU/ml -significant association with gestational HTN [p=0.041] and FGR[ p=0.082].
4 cases with euthyroid TPO positive status .[3 - h/o BOH/RPL with APLA positivity.Hhcy and GGI -2 pts.1 pt - prolonged period of infertility and GGI.

15. Trend in the reduction of MTA
Appropriate dose adjustment of L-Thyroxin in our study ->a trend towards reduction in mid trimester abortions[Odds Ratio 2.18( ;p=0.21) ; known to be significantly associated in the TPO pos hypothyroid women as ( study by Mandakini et al-2013)
Larger studies may be required for further extrapolation

16. CONCLUSIONS
Appropriate dose based adjustment of L-Thyroxin supplementation showed a trend towards decreasing the possibility of a midtrimester abortion.
Majority of the TPO pos women were subclinically hypothyroid .

17. TPO antibody levels more than 600IU/ml –significant associations with gestational HTN and FGR.
Pregnant women aged >30 yrs who were TPO pos -significant associations with Hhcy,APLA and BOH/RPL.

18. FUTURE RESEARCH
Surveillance & Management of Euthyroid TPO positive pregnant women.
TPO positivity and Cardiovascular disease-Preventive and Risk Modulation Strategies

19. ACKNOWLEDGMENT
Dr.Suresh K.P and Dr.Gautham T.Pranesh for reviewing the statistical results of the study. Dr. Govindarajan M J for his untiring personal and emotional support. ‘Pragmatism is good prevention for problems’ -Amit Kalantri Thanks

20. REFERENCES
Mandakini Pradhan, Bhavna Anand, Neeta Singh, Manasi Mehrotra. Thyroid peroxidase antibody in hypothyroidism: it’s effect on pregnancy. The Journal of Maternal Fetal and Neonatal Medicine, 2013; 26(6):
Alex Stagnaro-Green(Chair), Marcos Ablavich, Eric Alexander, Fereidoun Azizi, Jorge Mestman, Roberto Negro, Angelita Nixon, Elizabeth N. Pearce, Offie P. Soldin, Scott Sullivan, Wilman Wiersinga. Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and Postpartum.Thyroid.2011;21(10),

21. Gafoor F, Mansoor M, Malik T, malik MS, Khan AU, Edwards R, Akhtar W
Gafoor F, Mansoor M, Malik T, malik MS, Khan AU, Edwards R, Akhtar W. Role of thyroid in pregnancy. J Coll Physicians Surg Pak ;16:
Mannisto T, Vaarasmaki M, Ponta A, Hartikeinen AL, Rookonen A, Surcel HM, Bhoigu A, Jarvelin MR, Suvanto- Luukkonen E. Perinatal outcome of children born to mothers with thyroid dysfunction or antibodies. A prospective population based cohort study. J Clin Endocrinol Metab 2009;94;

22. Negro R, Formono G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H
Negro R, Formono G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H. Levothyroxin treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications. J Clin Endocrinol Metab 2006; 91:
Feki M, Omar S, Menif O, Tanfous NB, Slimane H, Zouari F, Rezigua H, et al. Thyroid disorders in pregnancy: frequency and association with selected diseases and obstetrical complications in Tunisian women. Clin Biochem 2008;

23. Casey BM. Subclinical hypothyroidism and pregnancy outcomes
Casey BM. Subclinical hypothyroidism and pregnancy outcomes. Obstet Gynecol 2005; 105:
Abbassi-Ghanavati M, Casey BM, Spong CY, Mc Intire DD, Halvorson LM, Cunningham FG. Pregnancy outcomes in women with thyroid peroxidase antibodies. Obstet Gynecol 2010;116(2 Pt 1):