HIV-positive women with a weak immune system more likely to have baby with growth retardation

HIV-positive pregnant women with a weak immune system have an increased risk of having an infant with intrauterine growth retardation, Thai investigators report in the April 1^st edition of the Journal of Acquired Immune Deficiency Syndromes.

Intrauterine growth retardation is associated with a number of serious illnesses in newborns. The investigators are hopeful that World Health Organization (WHO) guidelines recommending the use of combination HIV treatment by women with a CD4 cell count below 200 cells/mm³ will not only improve the health of women taking the treatment and help avoid mother-to-child HIV transmission, but also reduce the risk of intrauterine growth retardation.

Intrauterine growth retardation is defined as a birth weight below the tenth percentile for the corresponding gestational age – in other words, at the very lowest end of the expected range of weights for an infant. A less stringent definition is a birth weight below 2500g. Infants with intrauterine growth retardation have an increased risk of death. Poor nutrition and malaria are common underlying causes of intrauterine growth retardation in resource-limited settings. In richer countries, smoking is a common cause.

In 1987, the World Health Organization (WHO) estimated that almost one quarter of infants born every year in resource-limited settings have intrauterine growth retardation. The rate in Thailand in 1983 was 8.5%.

Thai investigators performed a retrospective study to identify the risk factors and prevalence of intrauterine growth retardation amongst the infants of mothers participating in a study into AZT treatment during pregnancy.

The study, called the Perinatal HIV Prevention Trial-1 was conducted between 1997 and 1999. The investigators’ analysis involved 1271 HIV-positive women, 58% of whom were pregnant for the first time. HIV treatment during pregnancy was restricted to AZT.

At the 26^th week of pregnancy, mean CD4 cell percentage was 20% (approximating to a CD4 cell count of 200 cells/mm³) and mean viral load was a little below 8000 copies/ml. Nearly all the women had either no or very mild symptoms of HIV infection. The rate of in utero (in the womb) HIV transmission was 2.7%.

A total of 7.6% of babies were born with intrauterine growth retardation and the mean birth weight was 2979g.

Statistical analyses were then used by the investigators to establish the factors associated with an increased risk of intrauterine growth retardation.

Their first analysis showed two HIV-related factors were important. The first was HIV transmission from mother-to-child in the womb (odds ratio [OR] 3.23, 95% confidence interval [CI], 1.23 to 8.12, p = o.01). CD4 cell percentage was also significant. Each 1% increment in CD4 cell percentage was associated with a significant reduction in the risk of intrauterine growth retardation (OR = 0.97, 95% CI, 0.94 to 0.99, p = 0.05).

However, in subsequent multivariate anaylsis that controlled for confounding factors, the only HIV-related factor associated with intrauterine growth retardation was CD4 cell percentage, with each 1% increase in CD4 cell percentage decreasing the risk of intrauterine growth retardation by 4% (OR = 0.96, 95% CI 0.93 to 0.99, p = 0.03).

Analysis showed that several maternal factors also increased the risk of intrauterine growth retardation. These included lower body mass index (BMI) (p = 0.01), body weight (p = 0.01) and height (p = 0.01).

Neither smoking nor drug use were risk factors for intrauterine growth retardation.

“The CD4 percentage was the main risk factor for intrauterine growth retardation in this population of HIV-infected pregnant women in Thailand,” comment the investigators.

They continue, “We have shown that a poor immune status is independently associated with a greater risk of intrauterine growth retardation in our cohort…this finding is important because all infants born to HIV-infected pregnant women with intrauterine growth retardation, infected or not…are at higher risk of mortality and morbidity.”

WHO guidelines for the prevention of mother-to-child HIV transmission recommend that combination HIV treatment should be taken during pregnancy if it is needed for the health of the mother. The CD4 cell threshold for the initiation of such treatment is currently 200 cells/mm³, which approximates to a CD4 cell percentage of 20%. The investigators suggest that HIV treatment during pregnancy “may also reduce the risk of intrauterine growth retardation”.