Factors associated with the risk of mother-to-child transmission

The overall risk of mother-to-child transmission is increased by a range of factors related to HIV disease, the mother, and the infant (for a comprehensive review of these factors see Newell et al., 1997). Some of these factors may also affect the risk of transmission through breast milk. Maternal risk factors include indicators of disease progression, such as high viral load, low CD4 count, and viral characteristics. The observation that the risk of transmission through breastfeeding is higher if the mother is infected postnatally (Dunn et al., 1992) suggests that the higher viral load associated with recent infection may also increase the risk of breastfeeding transmission. However, it is not clear whether viral load in blood and in breast milk are correlated. Viral load in the breast milk of postnatally infected women is an area that requires further study. Low CD4 counts have been associated with detection of HIV DNA in breast milk. A Kenyan study (Nduati et al., 1995) found a strong correlation between maternal immunosuppression (low CD4 counts) and the prevalence and concentration of breast milk HIV-1 DNA. However, knowledge of the role of maternal immunosuppression and advanced HIV disease in breast-milk transmission remains limited.

In a Malawi study of 338 women with HIV, 196 (58%) of whom were deficient in vitamin A, HIV transmission was significantly associated with vitamin A status, independent of maternal CD4 status (Semba et al., 1994). Vitamin A deficiency may increase the risk of mother-to-child HIV transmission by impairing T and B cell function, resulting in increased maternal viral load and reduced antibody concentrations. Alternatively, vitamin A deficiency could be a marker of advanced HIV disease, which may be the cause of the higher observed mother-to-child transmission rate. In a study of 72 women with CD4 counts of less than 400/ml in Nairobi (Nduati et al., 1995), vitamin A deficiency was associated with a linear increase in the prevalence of HIV-1 DNA in breast-milk cells. All six women with vitamin-A levels < 20 J_GO_KDG detectable HIV-1 DNA in their breast milk, compared to only three of eight women with vitamin-A levels at or above 40 J_GO_ Although the association between vitamin A and HIV in breast milk has been documented, no studies have been published concerning the role of vitamin A deficiency in breast-milk transmission. Vitamin A deficiency in HIV-infected women has been reported to be associated with fissured nipples (Nduati et al., 1997), which may facilitate transmission of HIV through breastfeeding. Poor breastfeeding techniques, especially poor attachment of the infant to the breast, may result in fissured nipples and hence HIV transmission may be prevented through breastfeeding counselling, and skilled help with positioning and attachment (Tess et al., 1998b; Van de Perre, 1992; Ekpini et al., 1997).

Table 3 Risk factors associated with increased overall risk of mother-to-child transmission

*Probably due to acquisition of further virus or minor trauma

See: Review Newell et al., 1997; and Kind et al., 1998; Mandelbrot et al., 1998; Read et al., 1998; Simonds et al., 1998; Bulterys et al. 1997, Burns et al.,1997; Coll et al., 1997; Ekpini et al.1997; Greenberg et al., 1997; Kuhn et al., 1997; Maguire et al., 1997; Matheson et al., 1997; Mayaux et al., 1997; Pitt et al., 1997; Shearer et al., 1997; Thea et al., 1997; Zollner et al., 1997; Dickover et al., 1996; Guay et al., 1996; Landesman et al., 1996; Lapointe et al., 1996; Lutz-Friedrich et al., 1996; Mandelbrot et al., 1996; Rodriguez et al., 1996; Shaffer et al., 1996; Wabire-Mangen et al., 1996; Harmsen et al., 1995; Matheson et al., 1995; Mayaux et al., 1995; Ometto et al., 1995; Temmerman et al., 1995; Borkowsky et al., 1994; Boyer et al., 1994; Burns et al., 1994; Dunn et al., 1994; Kliks et al., 1994; Lallemant et al., 1994; Nduati et al., 1994; Semba et al., 1994; Thomas et al., 1994; Clerici et al., 1993; Galli et al., 1993; Jackson et al., 1993; Lepage et al., 1993; Nair et al., 1993; Roques et al., 1993; Scarlatti et al., 1993; Scarlatti, Hodara et al., 1993; St Louis et al., 1993; Van de Perre et al., 1993; Villari et al., 1993; Dunn et al., 1992; European Collaborative Study, 1992; Goedert et al., 1991; Hutto et al., 1991; Lindgren et al., 1991; Monforte et al., 1991; Hira et al., 1990; Van de Perre et al., 1991; Tovo et al., 1988.

HIV has been recovered from vaginal and cervical secretions of pregnant women (Henin et al., 1993; John et al., 1997; Loussert-Ajaka et al., 1997) and from gastric secretions of infants born to HIV-seropositive women (Ait-Khaled et al., 1997; Nielsen et al., 1996). Delivery factors that increase contact between the infant and HIV-infected maternal body fluids (cervico-vaginal secretions and blood) may therefore be the mechanism for increased risk of transmission (Read et al., 1998; European Collaborative Study, 1994). Vitamin A deficiency may also be a co-factor for increased risk associated with delivery, through impaired integrity of epithelial surfaces (Bridbord and Willoughby, 1994) and increased vaginal viral shedding (John et al., 1997, Mostad et al., 1997).

Neonatal skin and mucous membranes are ineffective barriers against infective organisms. Direct invasion of the skin and oral and gastric mucosa by HIV may play a role in transmission from mother to child, including through breast milk. Traumatic or inflammatory disruption of the skin or mucous membranes may further increase the risk of transmission (Ekpini et al., 1997; Clerici et al., 1993; European Collaborative Study, 1992; Hutto et al., 1991; Goedert et al., 1989). Disruption of the epithelial integrity of the mucous membranes of the intestine or mouth, caused by nutritional factors or infection, may increase the risk of HIV transmission through breast milk.

Factors resulting in disruption of the integrity of infants' mucous membranes, such as oral thrush, may be associated with an increased risk of breast-milk transmission (Ekpini et al., 1997; Njenga et al., 1997; European Collaborative Study, 1992).

Feeding with cow's milk, allergic reactions to complementary foods, and infectious illness can all result in intestinal damage. Because damage to the epithelial integrity of the intestine may facilitate entry of HIV, mixed feeding might be more risky for HIV transmission than exclusive breastfeeding. Infants could thus be doubly disadvantaged by being at risk of HIV transmission through simultaneous exposure to HIV through breastfeeding, and the risks related to replacement feeding. Only three studies have compared the rate of transmission in exclusively breastfed, partially breastfed and formula-fed infants (Tess et al., 1998b; Bobat et al., 1997; Ryder et al., 1991;). Although the highest transmission rate was found in exclusively breastfed infants, the lowest rate in formula-fed infants, and intermediate rates in the mixed-feeding groups, the number of exclusively formula-fed or breastfed infants in these studies was small and the differences in rates of transmission were not statistically significant.