Premature and low birth weight babies becoming more frequent in HAART-treated mothers

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The frequency of premature deliveries and very low birth weight babies being born to HIV-positive mothers has increased significantly since the introduction of HAART in Europe, according to findings from the European Collaborative Study presented on Tuesday at the Eleventh Conference on Retroviruses and Opportunistic Infections in San Francisco.

The European Collaborative Study enrolled pregnant women at 25 clinical centres in nine European countries. This study looked at 4377 women who delivered infants prior to January 2004, and analysed the data in three time periods – 1994-97, 1998-2000 and 2001-2003.

The researchers, from the Institute of Child Health in London, looked at the proportions of infants delivered prior to 37 weeks of pregnancy (premature), and those delivered prior to 34 weeks of pregnancy (very premature). The study also looked at the proportion of infants with birth weights below 2500g (low birth weight) and 1500g (very low birth weight) in each time period, and analysed risk factors for prematurity and low birth weight.

Glossary

p-value

The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 

caesarean section

Method of birth where the child is delivered through a cut made in the womb.

multivariate analysis

An extension of multivariable analysis that is used to model two or more outcomes at the same time.

mother-to-child transmission (MTCT)

Transmission of HIV from a mother to her unborn child in the womb or during birth, or to infants via breast milk. Also known as vertical transmission.

combination therapy

A therapy composed of several drugs available either as separate tablets, or as fixed-dose combination (FDC).

In the period 1995-97, 5.94% of infants were born prior to 34 weeks of pregnancy; by 2001-2003, this proportion had risen to 21.2% (p=0.0001). The proportion delivered prior to 37 weeks grew similarly, from 17.1% in 1995-97 to 46.1% in 2001-3 (p=0.0001).

The proportion of very low birth weight babies grew from 0.48% in 1995-97 to 8.05% in 2001-3, and the proportion of low birth weight babies grew from 14.9% to 36.9% in 2001-3.

For each measure, the proportion in the period 1998-2000 was midway between the two.

Risk factors for premature delivery were found to be age greater than 35 years (OR 2.24, p=0.002), injecting drug use during pregnancy (OR 2.52, p=0.0001), baseline CD4 cell count below 200 (OR 2.36, p=0.0001) and protease inhibitor-containing HAART during pregnancy (OR 4.17, p=0.0001). Women already taking HAART when they became pregnant, or who commenced HAART in the first three months of their pregnancy, had a significantly higher risk of premature delivery.

Infant deaths occurred at a much higher rate than the population average in western Europe, with evidence of a trend towards a higher death rate in the period after 2000 (21.0 per 1000 births in 1999-2000 versus 24.5 per 1000 in 2001-2). The European range is 4.4 - 9.2 deaths per 1000 births in HIV-negative women. Although the number of neonatal deaths was too small for a multivariate analysis to tease out risk factors, 74% of deaths occurred in premature infants, and the median length of gestation of infants that died was 28 weeks.

A US review of the Antiretroviral Pregnancy Registry presented in the same session of the conference found a moderately increased risk of premature delivery in protease inhibitor-treated mothers, but the authors concluded that it was impossible to tell whether premature delivery was driven by protease inhibitor treatment, since women receiving protease inhibitor treatment were more likely to have low CD4 cell counts. Advanced HIV disease might have some bearing on the risk of premature delivery, argued Karen Beckerman of New York University, presenting the data.

However, the study also found that mothers exposed to PI treatment during the first or second trimester, or already receiving such treatment when they became pregnant, were significantly more likely to deliver prematurely.

Dr Annemiek De Reuter of St Thomas’s Hospital told aidsmap: “I think these data emphasise the importance of carefully weighing up the respective risks and benefits of using HAART or using AZT and caesarean section in mothers with HIV.”

She also drew attention to findings from Barcelona which show a higher incidence of pre-eclampsia in pregnant HIV-positive women since the introduction of HAART, suggesting that a possible connection between pre-eclampsia and prematurity in HIV-positive pregnant women who receive HAART deserves further investigation.

Current treatment guidelines in the UK suggest that HAART should be used in pregnant women only where the mother’s health warrants it, and that AZT and caesarean section should otherwise be used in mothers with lower viral loads (below 10,000 copies/ml and CD4 count above 250 cells/mm3. A recent report in the journal AIDS showed that mother-to-child HIV transmission had declined to very low levels since this regimen was implemented in London clinics.

Further information on this website

UK guidelines on treatment during pregnancy

Combination therapy during pregnancy - overview of research to date

References

Beckerman K et al. Association between antiretroviral therapy during pregnancy and prematurity/low birth weight. Eleventh Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 97, 2004.

Thorne C et al. Pregnancy outcome in ART-treated HIV-infected women in Europe. Eleventh Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 98, 2004.