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The role of transplacental microtransfusions of maternal lymphocytes in HIV transmission to newborns

Khan, Omar A

doi: 10.1097/QAD.0b013e328314e394
Clinical Science: Editorial Comment

University of Vermont College of Medicine, Burlington, Vermont, USA.

Received 14 April, 2008

Accepted 18 April, 2008

Correspondence to Omar A. Khan, MD, MHS, Attending Physician, Christiana Care Health System and A.I. duPont Hospital for Children, 1309 Veale Road, Suite 11, Wilmington, Delaware 19810, USA. E-mail:

More than 2.5 million children are presently infected with HIV, and it is a fair statement that mother-to-child transmission (MTCT) is the predominant mode [1,2]. It represents a significant issue to say the least; these 2.5 million are the most vulnerable, and their health status affects not only them but also their families and society. In addition, the fact that high rates of perinatal transmission occur in developing settings (disproportionately in sub-Saharan Africa) amid the presence of HAART available in developed settings, makes it not only a development imperative but an ethical and human rights one.

Biggar et al. [3] present a study which is perhaps more interesting for its methods than its conclusions – a slightly unusual occurrence. It is essentially a negative study – a refreshing change – but the information presented is nonetheless useful and thought provoking. The authors developed a method to assess ‘microtransfusions’ from mother to baby during the delivery process, and attempted to correlate this with infection risk. They did so by looking for maternal blood cells in cord blood. Although the technique they describe using dried blood spots seems adequately sensitive (one in 1000) for the level of analysis they were looking for, the authors correctly point out that it is challenging to pick out the signal of fetal blood cells against the background noise of maternal blood cells, when the signal and background are genetically similar.

The authors discarded samples from infants found to be HIV positive from cord blood samples, surmising these individuals were infected in utero. They focused their attention instead on those found to be HIV negative in cord blood at birth, and HIV positive at 4–8 weeks. The authors hypothesized these infants acquired HIV perinatally, and sought to validate this by looking at maternal blood microtransfusions in the cord blood. They identified 18 appropriate infants (i.e. infants with likely perinatal transmission) and found maternal blood in nine (50%) of those infants. However, they also found maternal blood in 19 out of 43 controls (44%). Therefore, they concluded, perinatal transmission occurred independent of detectable maternal cells in the cord blood, and vice-versa.

The study is notable for explicating an interesting technique to assess maternal blood transfer (details are included in the main article). However, it might make too little of another logical source of MTCT, that is, breastfeeding. The authors cite studies in which the transmission rate among breastfed and bottlefed infants was similar [4]; they also suggest a rate of 0.5–1% risk of transmission per month of breastfeeding [5,6]. However, this assertion is neither unequivocally nor universally accepted. Coovadia et al. [4] actually found HIV acquisition for mixed (nonexclusive) breastfeeding was around 6%. Earlier works by Fawzi et al. [7] and Piwoz et al. [8] have found a significant rate of transmission of HIV-1 via breastfeeding (it seems to vary by exclusive or nonexclusive breastfeeding, and of course by maternal viral load, CD4 cell count and other maternal factors). A more recent study [9] found a postnatal HIV transmission rate via breastfeeding to be 8.2%. Others suggest an even stronger relationship between breastfeeding and HIV, and have advocated for a variety of prevention and control strategies in response [10].

For now, breastfeeding remains the supported choice in resource-poor settings due to the array of protective benefits of breastfeeding on HIV-related and non-HIV-related health concerns. It is not a straightforward recommendation, however, and the data are evolving as to what exact regimen of breastfeeding to recommend, depending on the patient's resource environment [which includes access to antiretroviral therapies (ARTs)]. Furthermore, and not without controversy, authorities recommend no breastfeeding by HIV-infected mothers in developed settings [11,12].

Regardless of the exact role that breastfeeding plays in transmission – and there are studies to support a variety of figures along a continuum – there are other possibilities to consider for those infants born HIV negative but becoming HIV positive at 4–8 weeks. Biggar et al. [3] note the high sensitivity of the PCR-based testing method utilized for cord blood testing, but it is possible (although admittedly not likely) that late transplacental transmission to the fetus could result in a negative test at birth but a positive one subsequently, at the 4–8-week testing mark. Swallowing HIV-infected fluid during delivery has also been described as a possible source [13,14], and is a possibility, which would not be detected by the authors' testing methods.

The study was conducted in a setting in which, according to the authors, maternal ARTs are not used. The clinical reality is that perinatal infection continues to occur in the face of prevention efforts, which makes it imperative that access to treatment be expanded. Indeed, access to perinatal treatment regimens (and ART breastfeeding regimens currently under study) should render the point moot as to when exactly HIV transmission occurs in the birthing process and early infant stages. Recent studies have borne out efficient, locally appropriate treatment strategies for mother and child, which significantly decrease HIV risk [15,16] and must further be validated in other settings. Ultimately, this paper is more useful as a methodology description, and can likely be utilized in other, non-HIV settings in which assessment of maternal blood exchange would be important. What it highlights – intentionally or not – to the scientist also interested in clinical care, human rights, and ART policy, is that a response to the underlying problem is long overdue.

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