No More Stillbirths 

Low doses of aspirin 
can combat miscarriages, says Biplab Das 

Giving birth to a dead child is the worst nightmare that a pregnant woman can have. And sometimes, this nightmare turns into reality, shattering her desire to become a mother. At the onset of pregnancy, many women develop deadly antibodies that bring about early foetal loss. Among these, antiphospholipid antibodies have been the focused area of study of a research team led by L. Regan, professor of obstetrics and gynaecology at the Imperial College School of Medicine, St Mary's, London. 

In the February issue of the British Journal of Obstetrics and Gynaecology, Regan and his colleagues have reported that treatment with low doses aspirin and heparin (a chemical that prolongs blood clotting) help women who have had recurrent miscarriages and avert early pregnancy loss. 

The tissue analysis of the aborted foetal cells shows that antiphospholipid antibodies jam the uteroplacental blood vessels resulting in thrombosis or clotting of blood, which leads to malfunctioning. 

Recent in vitro studies reveal that these antibodies directly hamper the function of trophoblasts (cells which attach the fertilized ovum to the uterine wall), giving rise to improper implantation of the fertilized ovum. 

But, with aspirin and heparin treatment, these physiological anomalies have been overcome to a great extent. Antiphospholipid antibodies-positive women taking aspirin showed increase in live birth rate upto 40 per cent. When low-dose aspirin was used with heparin, live birth rate in those women increased to 70 per cent. 

Initially, the research team wanted to know how the women with antiphospholipid antibodies would respond to low-dose aspirin and heparin. In search of clinical evidence, Regan's team selected 150 pregnant women with a history of miscarriages. All of them tested positive for antiphospholipid antibodies. 

After urine pregnancy tests were positive, all the women were given a low dose of aspirin (75 mg daily). During a five-week observation period, ultrasound scans were taken to detect fetal heart activity. As fresh heart started to beat, heparin was given. Of the 150 women, first 97 were given calcium heparin and others were treated with low molecular-weight heparin, enoparin sodium (20 mg daily). 

During this course, both the mother and fetus were carefully observed. From the 24th week, all the pregnant women underwent regular ultrasound scans to monitor fetal growth. Before the fetus turned 34 weeks, they were put under a special bi-weekly observation programme. 

As long term heparin treatment can develop thrombocytopenia (decrease in number of platelets) and osteopenia (reduction in bone mass), four weekly platelete count and dual x-ray bone densitometry of lumber spine, and other tests were performed on the 12th and 34th week of pregnancy and also after the birth of the child. 

After 34 weeks of pregnancy, both aspirin and heparin were taken off. For Regan and his teammates, the results were encouraging. The live birth rate increased to 71 per cent among the 150 women, while 41 pregnancies did not progress beyond 24 weeks. As many as 108 pregnancies passed the barrier of 24 weeks. 

Of the 108 pregnancies, 26 faced premature delivery. And the remaining one died before 24 weeks. The infants born had an average birth weight of 3.069 kilograms. So in vitro studies bolstered by clinical evidence suggest that fetal loss in women with antiphospholipid antibodies has a thrombotic base. 

Moreover, the research team found an anti-coagulant called annexin V in low density among women with antiphospholipid compared with both controls and antiphospholipid antibodies-negative women with a history of miscarriages. 

Annexin V latches on to phospholipid's anionic surface making them non-thrombogenic. It has also been found that antiphospholipid antibodies in excess decrease annexin V in the region of placental villi (finger like projection). In mice, studies reveal antiphospholipid antibodies' implication in the faulty development of trophoblast, which ultimately manifests in pregnancy loss. 

Furthermore, other mice studies revealed clues to different route of antiphospholipid antibodies apart from thrombosis in disrupting trophoblast's function. As an antidote, aspirin halts the thrombosis in placental blood vessels by stalling the action of cyclo-oxygenase in platelets. Using heparin in conjunction with aspirin proves more effective. 

Since heparin protects trophoblast phospholipids from the attack of antiphospholipid antibodies, it prevents thrombsis. However, Regan and his colleagues' work remains inconclusive. Nevertheless, it provides hope for those anxious women who have already experienced a miscarriage.