Role of Antiphoso lipid anti-bodies and Antinuclear anti-bodies in pregnancy outcome and its treatment for better outcome

 

Alka Dani¹, Abhishek^2*

 

Abstract              Background: Patients with raised titre of ANA antibodies and APLA during pregnancy have more guarded prognosis like recurrent pregnancy loss, preterm delivery, lUGR, oligohydramnios, stillbirth and maternal complications like severe rhehmatoid arthritis, SLE,lTP, rashes, multiorgan failure in cases of positive ANA test and severe preeclampsia, venous and arterial thrombosis, stroke, coronary artery thrombosis if APLA is positive. Aims and objectives: In this study our objectives are to assess the role of ANA and APLA on maternal and fetal health and to diagnose and treat the condition early in pregnancy to improve the outcomes. Material and Methods: In this study 55 cases with h/o RPL and adverse maternal and fetal outcome in previous pregnancies and subchorionic haemorrhage in first trimester during current pregnancy were studied for presence of ANA, LAC and ACLA and their titers and serial sonography was done. Patient's councelling and treatment started accordingly and test was repeated after 12weeks and maternal and fetal outcome was noted and analysed. Result- Out of 55patients 63.6% were ANA+ positive and 29.1% were ANA2+ positive. ACLA was positive in 12.7% and LAC in 3.3% of patients. 38.2% of patients had PIH, 20% GDM, 20% hypothyroidism and12.7% patients had hyperthyroidism. In 63.6% patients, USG findings were abnormal. 78.2% patients had good fetal outcome while 21=8% patients had poor fetal outcome. Conclusion: ANA and APLA test should not be done as a routine but only in risk cases for early detection and prompt treatment so as to improve pregnancy course and fetal outcome.

Keywords: Recurrent pregnancy loss, Antinuclear antibodies, Antiphospholipid antibodies.

 

INTRODUCTION

Patients who have raisedtitre of antinuclear anti-bodies (ANA) and antiphosolipid anti-bodies(APLA) during pregnancy have a more guarded prognosis like recurrent miscarriage, pre-term delivery, intra-uterine growth retardation (IUGR), oligohydramnios, still birth and maternal complications like severe rheumatoid arthritis, SLE, auto immune thrombocytopenia, rashes and multi-organ failure in case of positive ANA test and severe pre-eclampsia, venous and arterial thrombosis, stroke, coronary artery thrombosis if APLA is positive. APLA includes lupus anticoagulant (LAC) AB and anticardolipin (ACL) AB. Incidence of LAC in India is 15-30% and ACL is 23-86%. These patients are more likely to get benefitted by therapeutic interventions like Aspirin, Heparin and Prednisolone. The ANA Test was designed by Dr. George Friou in 1957. It can also refer to as fluorescent antinuclear anti-body test (FANA). It is a sensitive screening test used to detect autoimmune diseases. ANA can be found in approximately 5% of normal population in low titers. ANA titer of <= 1:40 are considered negative. Those with higher titers have been found to have a risk of RPL and are more likely to be benefitted from Prednisone. In 1983 Hughes first described patients with the combination of clinical features (i.e. thrombosis, thrombocytopenia, RPL, IUGR, pre-eclampsia) associated with the presence of APLA and LAC. Primary method of diagnosis requires clinical and laboratory findings with the clinical criteria and should be tested for both LAC and ACL immunoglobulins (IgG and IgM).

Patho-physiology:

Human APLA reacts with endothelial structures^[1] which disturbs the PGE₂/Thromboxane production balance², interaction with platelet PLs with consequent upregulation of platelet aggregation^[3], dysregulation of compliment activation and^[4] interaction of APL with phosphatidyl serine expose during trophoblast syncytium formation resulting in more direct effect of APLA on placental structure.

APS is associated with increased maternal morbidity and mortality as well as increased perinatal MMR. It is associated with increased risk of venous and arterial thrombosis, coronary artery occlusion. There is increased incidence of pre-eclampsia usually before 34 weeks, pre-mature deliveries, infertility, spontaneous abortion and still births. MOFD has been described during pregnancies by Asherson^[1] and during puerperium by Kochenom.² Neonatal morbidity and mortality is due to severe pre-eclampsia and IUGR. Rate of fetal loss can be reduced by 20% by therapy (Aspirin and Heparin) as described by Cowchok et al³.

Aims and Objectives

To assess the role of Antinuclear antibody and Antiphospholipid antibody on maternal and fetal health. To diagnose and treat the condition early in pregnancy to improve outcomes.  To study relation of relative titers of ANA with other anti-bodies and with adverse pregnancy outcomes.

 

MATERIAL AND METHODS

RESULTS

Table 1: Descriptive Statistics of Demographic Variables

 

Table 2: Distribution of study group as per history of Hypertension

 

Table 3: Distribution of study group as per history of Diabetes

 

Table 4: Distribution of study group as per Thyroid function test

 

 

Table 5: Distribution of study group as per result of ANA

 

Table 6: Distribution of study group as per result of ACL

 

Table 7: Distribution of study group as per result of AL

Table No 8: Distribution of study group as per USG finding

 

Table No 9: Distribution of study group as per history of Treatment taken

 

Table 10: Distribution of study group as per outcome of pregnancy

 

Table 11: Distribution of study group as per IUFD

Table 13: Association USG variable with other Parameters

Parameters	USG			Chi square Test	P-Value	Significant at 5% Level
	Abnormal	Normal	Total
HTN
PIH	14	7	21	0.135	0.714	No
No	21	13	34
Total	35	20	55
Diabetes MOD
GDM	7	4	11	0.000	1.000	No
No	28	16	44
Total	35	20	55
Thyroid function test
Hypothyroidism	8	3	11	0.555	0.758	No
Hyperthyroidism	4	3	7
No	23	14	37
Total	35	20	55
ACL
Negative	29	19	48	1.690	0.194	No
Positive	6	1	7
Total	35	20	55
Treatment taken
Yes	22	17	39	3.025	0.082	No
No	13	3	16
Total	35	20	55
LA
Negative	33	20	53	1.186	0.276	No
Positive	2	0	2
Total	35	20	55
Outcome
Good	24	19	43	5.211*	0.022	Yes
Bad	11	1	12
Total	35	20	55

*Statistically Significant at 5% level i.e., P<0.05 .

Table 14: Association Outcome variable with other Parameters

Parameters	Outcome			Chi square Test	P-Value	Significant at 5% Level
	Bad	Good	Total
HTN
PIH	2	19	21	3.010	0.083	No
No	10	24	34
Total	12	43	55
Diabetes MOD
GDM	1	10	11	1.306	0.253	No
No	11	33	44
Total	12	43	55
Thyroid function test
Hypothyroidism	5	6	11	5.739	0.057	No
Hyperthyroidism	0	7	7
No	7	30	37
Total
ACL
Negative	10	38	48	0.214	0.643	No
Positive	2	5	7
Total	12	43	55
Treatment taken
Yes	2	37	39	21.892*	<0.001	Yes
No	10	6	16
Total	12	43	55
LA
Negative	12	41	53	0.579	0.447	No
Positive	0	2	2
Total	12	43	55

*Statistically Significant at 5% level i.e., P<0.05 .

In this study of 55 patients average age of patients was between 20_42 years with a mean of 30. Average of married life was between 1_12yr with a mean of 4.45yr. 38.2% patients had PIH, 20% patients had GDM, 20% patients had hypothyroidism, 12.7% patients had hyperthyroidism. In 63.6% patients USG findings were abnormal (IUGR, Oligohydramnios, IUFD,). ANA1+ was present in 63.6% of patients, ANA2+ was present in 29.1%,ACLA in 12.7% patients and LAC in 3.3% patients. 78.2% of patients had taken treatment and 78.2% patients had good fetal outcome while 21.8% patients had bad fetal outcome and12.7% ended up with IUFD or missed abortions. Those who were ANA 1+ or 2+ positive, 40% and 37.5% patients had PIH respectively with p value of 0.84 which is not significant statistically. 20% and 12.5% patients had GDM with ANA+ and ANA2+ respectively with p value of 0.245 (not significant) 11.42% and 43.75% patients had hypothyroidism in presence of ANA+ and ANA2+ respectively and hyperthyroidism was present in 14.2% and 12.5% of patients respectively with p value of 0.052 which is not significant statistically. Abnormal USG findings were present in 57.14% and 81.25% of patients with ANA+ and ANA 2+ positive patients respectively with p value of 0.212 (not significant). 72.14% patients with ANA+ and 68.75% patients with ANA 2+ had taken treatment. Bad fetal outcome was 20% and 31.25% in ANA+ and ANA 2+ positive patients respectively with p value of 0.364 (statistically not significant). 8 patients were APLA (ACL antibodies + LA antibodies) positive, out of which 25% had PIH, 12.5% had GDM, and 25% had hypothyroidism. It was found that 63.6% patients had abnormal USG findings, 21.8% patients had bad fetal outcome and 70.9% patients had taken treatment. It was also observed in this study that multiparae(>1 issue) and married life 5 or more years, had better prognosis. P values of these parameters is 0.018 and 0.024 respectively which is statistically significant. Bad fetal outcome in presence of PIH with APLA positive patients was16.6%, in GDM patients, 8.33%, in hypothyroidism patients 41.66%, hyperthyroidism patients 0 %, in patients with abnormal USG findings 31.42% and in those who had not taken treatment it was 83.33%. Significant impact on pregnancy outcome was associated with abnormal USG findings and treatment taken or not. P value of these parameters are 0.022 and 0.001 which is statistically significant.

 

DISCUSSION

Association of APLA with adverse pregnancy outcome is documented since long however association of ANA with recurrent pregnancy loss or adverse course during pregnancy is still debatable. Kutteh WH et al from USA in1996found that 17.3% patients with recurrent pregnancy loss(RPL) had positive ACLA, 10.1% women were positive for another APLA ⁵ while in our study it was 16%.Kumar KSD et al from India in 2002 reported importance and usefulness of screening of APLA in women experiencing RPL as a mandatory routine for instituting efficient therapeutic regimen for a successful outcome of pregnancy (6),in this study successful outcome. S Velayuthaprabhu et al from India in 2005 reported that levels of aCL IgG and aPS IgG were detected as 40% and 19% respectively in women with history of recurrent abortions (7). Rosalind et al from Pittsburgh found that previous adverse pregnancy outcome was the most important risk factor for an adverse outcome in subsequent pregnancy ⁸. Luis H. et al in 1992 reported that efficacy of treatment with prednisolone and aspirin in cases of RPL with the antiphospholipid syndrome. They found that prior to therapy, the rate of live-born babies was 15.6% , and after therapy, it was 100%. In this study we also got 100% successful pregnancy outcome. There was no significant adverse effects on either mother or babies⁹.In May 1999 J Associate Physician ( authorized by Chakraborty S, Bhunia C, Bhattacharya DK, ) recommended that detection of APL antibodies must be considered in women with previous pregnancies complicated by unexplained fetal wastages ¹⁰.Giasuddin et al from Bangladesh reported in 2010 that prevalence of ACA in patients with recurrent pregnancy loss was37.1% while in control group it was 5.4%¹¹.

 

CONCLUSION

From this progressive case study we conclude that ANA and APLA should not be done as a routine but only in risk cases and in patients with poor pregnancy outcome in previous pregnancies as to improve pregnancy course as well as outcome.

 

REFERENCES

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2. Kochenour NK, Branch DW, Rote NS, et al. A new postpartum syndrome associated with antiphospholipid antibodies. Obstet Gynecol. Mar 1987; 69(3 Pt 2):460-8. 
3. Cowchock FS, Reece EA, Balaban D, et al. Repeated fetal losses associated with antiphospholipid antibodies: a collaborative randomized trial comparing prednisone with low-dose heparin treatment. Am J Obstet Gynecol. May 1992;166(5):1318-23. 
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8.    Rosalind Ramsey-Goldman¹,², Joan E. Kutzer¹, et all Pregnancy Outcome and Anti-Cardiolipin Antibody in Women with Systemic Lupus Erythematosus, Am. J. Epidemiol. (1993) 138 (12):1057-1069.
9. Luis H. Silveira, M.D.Chris L. Hubble, et all American Journal of Medicine Volume 93, Issue 4 , in October 1992 published a paper on Prevention of anticardiolipin antibody-related pregnancy losses with prednisone and aspirin.
10. Chakrabarti S, Bhunia C, Bhattacharya DK, The prevalence of antiphospholipid antibodies in cases of recurrent pregnancy loss, J Assoc Physicians India. 1999 May; 47(5):496-8.
11. Giasuddin AS, Mazhar I, Haq AM Prevalence of anticardiolipin antibody in Bangladeshi patients with recurrent pregnancy loss, Bangladesh Med Res Counc Bull. 2010 Apr;36(1):10-3.

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