BHIVA: HIV-positive women at increased risk of late pregnancy loss

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HIV-positive women appear to be between two and four times as likely as HIV-negative women to experience late pregnancy loss, according to a retrospective notes review from an east London HIV clinic presented to the 14th Annual British HIV Association (BHIVA) Conference last month in Belfast.

A 2004 study from Uganda found that the risk of miscarriage was five times higher in asymptomatic HIV infection compared with HIV-negative women. And yet, despite increasing numbers of pregnant women living with HIV in UK – in 2007, 794 HIV-positive women were known to be pregnant – there are few data on pregnancy loss in HIV-positive women.

Consequently, investigators from Homerton University Hospital in east London undertook a retrospective notes review of HIV-positive women attending for antenatal care between 2000 and 2007, looking at rates of late pregnancy loss.

Glossary

retrospective study

A type of longitudinal study in which information is collected on what has previously happened to people - for example, by reviewing their medical notes or by interviewing them about past events. 

antenatal

The period of time from conception up to birth.

asymptomatic

Having no symptoms.

cervix

The cervix is the neck of the womb, at the top of the vagina. This tight ‘collar’ of tissue closes off the womb except during childbirth. Cancerous changes are most likely in the transformation zone where the vaginal epithelium (lining) and the lining of the womb meet.

inflammation

The general term for the body’s response to injury, including injury by an infection. The acute phase (with fever, swollen glands, sore throat, headaches, etc.) is a sign that the immune system has been triggered by a signal announcing the infection. But chronic (or persisting) inflammation, even at low grade, is problematic, as it is associated in the long term to many conditions such as heart disease or cancer. The best treatment of HIV-inflammation is antiretroviral therapy.

They examined late pregnancy loss – defined as 14 weeks and beyond – because approximately 25% of all pregnancies miscarry in the first trimester, often undetected, and many women will not present for antenatal care earlier than 14 weeks.

There were a total of 242 pregnancies during the study period, of which 19 pregnancies (in 18 women) resulted in late pregnancy loss: a rate of 8%.

Maternal characteristics

The age of the women who experienced late pregnancy loss ranged between 23.3 and 39.4 years, and the average age was 31.6 years.

All but four of the women (78%) were born in sub-Saharan Africa and eleven of the women (61%) were of uncertain immigration status. In addition, seven (39%) had documented psychosocial problems, such as intimate partner violence and severe financial difficulties. “This,” noted the investigators, “was a reflection of the complex relationship between HIV, migration and gender which often manifests in severe social vulnerability.”

Just over half of the women (10; 56%) were newly diagnosed with HIV during this pregnancy and most (74%) had asymptomatic HIV disease. The mean CD4 nadir was 327 cells/mm3 and the mean CD4 count at loss was 393 cells/mm3. Most of the women had moderate HIV RNA levels (38% below 400 copies/ml, 56% between 400 and 100,000 copies/ml.).

Just under half (8; 42%) were on potent antiretroviral therapy (two on NNRTI-based ART and six on PI-based ART). Half of the women on ART commenced treatment before, and half after, conception.

Eight (42%) of the women had experienced previous pregnancy loss. Two women were documented smokers and three were co-infected with hepatitis B virus, but there was no history of injecting drug use or heavy alcohol use in any of the women.

Foetal loss data

Fifteen pregnancy losses were due to late miscarriages, and four were intrauterine deaths.

The gestational age at loss ranged between 14 and 39 weeks, with a median of 18 weeks.

A total of 14 women consented to postmortem, where the overwhelming (10; 70%) cause of death was found to be chorioamnionitis (inflammation of the membrane covering the foetus) which is usually caused by a bacterial infection ascending from cervical-vaginal regions.

Previous studies have suggested an increased risk of chorioamnionitis linked to bacterial vaginosis in HIV-positive pregnancy, although this has generally been associated with in utero transmission.

Although the cause is unclear, say the investigators, it is thought that the cumulative immunosuppressive effects of HIV and pregnancy may result in increased ascending vaginal infections.

Sexual health screening recommended

Only six of the ten women whose foetal cause of death was chorioamnionitis had previously undergone sexual health screening during their pregnancy (although no infections were found in these six).

The investigators note that out of all pregnancy losses, sexual health screening was performed in only 53% of cases, and they point out that current BHIVA guidance recommends that all women are screened for sexually transmitted infections as early as possible into their pregnancy.

Although there was no comparative control group, making it difficult for the investigators to come to overarching conclusions, they note that an 8% pregnancy loss rate is "high", given that the rate is 2% in the general HIV-negative population, and 4% in HIV-negative women in east London.

Their study highlights that women living with HIV may be at a higher risk of experiencing pregnancy loss than the general population. The reasons for this are unclear, however, and they concluded by advocating for large-scale prospective data collection on HIV and pregnancy loss in "this under-investigated area".

References

Evans-Jones R et al. Pregnancy loss in HIV-positive women attending antenatal care at a London centre. Fourteenth BHIVA Conference, Belfast. Abstract O14, 2008.