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Risk Factors for Mother-to-Child Transmission
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Risk Factors for Mother-to-Child Transmission
Viral load (HIV-RNA level)
Genital tract viral load
CD4 cell count
Clinical stage of HIV
Unprotected sex with multiple partners
Smoking cigarettes
Substance abuse
Vitamin A deficiency
STDs and other coinfections
Antiretroviral agents
Preterm delivery
Placental disruption
Invasive fetal monitoring
Duration of membrane rupture
Vaginal delivery vs. cesarean section
Breastfeeding
Table 28
Factors affecting mother-to-child transmission of HIV-1
| VIRAL | Viral genotype and phenotype Viral resistance Viral load |
| MATERNAL | Maternal immunological status Maternal nutritional status Maternal clinical status Behavioural factors Antiretroviral treatment |
| OBSTETRICAL | Prolonged rupture of membranes (> 4 hours) Mode of delivery Intrapartum haemorrhage Obstetrical procedures Invasive fetal monitoring |
| FETAL | Prematurity Genetic Multiple pregnancy |
| INFANT | Breastfeeding Gastrointestinal tract factors Immature immune system |
Viral load
Transmission is increased in the presence of high levels of maternal viraemia. The local viral load in cervico-vaginal secretions and in breast milk may also be an important determinant of transmission risk intrapartum and through breastfeeding. The presence of sexually transmitted diseases or other causes of inflammation, vitamin A deficiency and local immune response may affect viral shedding.
Different viral phenotypes show differing tissue tropism. Macrophage-tropic non-syncytium-inducing (NSI) viral isolates appear to be preferentially transmitted to children even when the dominant maternal strains are syncytium inducing (SI). There may be a difference in disease progression for the child related to the viral strain. Rapid/high virus isolates have been associated with transmitting mothers whereas slow/low virus isolates were associated with non-transmitting mothers.
Maternal factors
Transmission from mother to child is more likely with decreased maternal immune status, reflected by low CD4+ counts, low CD4+ percentages or high CD4+/CD8 ratios. Maternal nutritional factors: low level of serum vitamin A in HIV-1 positive mothers have been correlated with higher risk and rate of transmission. Several behavioural factors have been associated with an increased rate of transmission from mother to child. These include cigarette smoking and maternal hard drug use. Unprotected sexual intercourse during pregnancy has been linked to an increased risk of motherto-child transmission. Placental infections and non-infectious conditions such as abruptio placentae have also been implicated in transmission of the virus from mother to child.
Obstetric factors
With the majority of mother-to-child transmission occurring at the time of labour and delivery, obstetric factors are important determinants of transmission. Suggested mechanisms for intrapartum transmission of HIV-1 include direct skin and mucous membrane contact between the infant and maternal cervico-vaginal secretions during labour, ingestion of virus from these secretions, and ascending infection to the amniotic fluid. Preterm delivery, intrapartum haemorrhage and obstetric procedures (use of fetal scalp electrodes, episiotomy, vaginal tears and operative delivery) were related to transmission risk. Prolonged rupture of membranes has been associated with increased risk of transmission in a number of studies and is an important risk factor.
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Fetal factors
Fetal genetic factors may play a part in transmission. Little is known yet about the role of genetic factors such as the CCR-5 delta32 deletion and HLA compatibility of mother and infant in the determination of transmission risk, but it is known, that concordance between infant and maternal HLA has been associated with increased risk of transmission. Preterm infants have higher reported rates of transmission of HIV-1 in several studies. The higher rates of infection seen in first-born twins. This effect is more pronounced in vaginally delivered twins, where a two fold increase in infection is seen in first born twins than second born, but is also present in twins delivered by cesarean section Other fetal factors may include co-infection with other pathogens, fetal nutrition and fetal immune status.
Infant factors
Breastfeeding is responsible for a high proportion of mother-to-child transmission in developing countries, where 30% or more of perinatal HIV infections will occur through breast milk. This is less common in the developed world, where most HIV-positive women will not breast feed. Breast milk contains both cell associated and free virus, the amount of which may be related to the immune suppression of the mother and vitamin A levels. Other protective factors are also present in breast milk, including mucins, HIV antibodies, lactoferrin, and secretory leukocyte protease inhibitor (SLPI). The risk of breast milk transmission may also depend upon other factors, such as maternal disease stage, breast abscesses, mastitis, nipple cracks, maternal Vitamin A and oral thrush in the child. The risks of postnatal transmission may also be related to other factors in the newborn. HIV entry may occur through the gastro-intestinal tract following ingestion of virus in utero or at birth. There is decreased acidity, decreased mucus, lower IgA activity and thinned mucosa in the newborn gastro-intestinal tract, which may facilitate transmission. The newborn immune system may also be deficient in macrophage and T cell immune response, increasing the susceptibility to infection.
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