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                OPINION

                HOW CAN WE REDUCE THE RISK OF MOTHER-TO-CHILD TRANSMISSION OF HIV DURING INVASIVE OBSTETRIC PROCEDURES?

                C N Mnyani1, BA, MB ChB, FCOG 
            

            E Nicolaou2,3, MD, FCOG, Dip Fet Med

            E Bera4, MB BCh, FCOG
        

        V Black5, BSc, MB BCh

        JC Hull3, MB BCh, MRCOG, FCOG, DTM&H

        J A McIntyre1,6, MB ChB, FRCOG

        1Anova Health Institute, Johannesburg

        2Maternal Fetal Medicine Centre, Morningside MediClinic, University of the Witwatersrand, Johannesburg

        3Department of Obstetrics and Gynaecology, Chris Hani Baragwanath Academic Hospital, Johannesburg

        4Department of Obstetrics and Gynaecology, Rahima Moosa Mother and Child Hospital, University of the Witwatersrand, Johannesburg

        5Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg

        6Centre for Infectious Diseases Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town

    

    
        Antenatal invasive obstetric procedures may be diagnostic or
        therapeutic, and are performed at different stages of pregnancy for
        various indications. The most common indication for an invasive
        procedure during pregnancy is for fetal karyotyping when a chromosomal
        abnormality or a genetic defect is suspected, either from the
        couple’s history or from ultrasound assessment of the fetus.
        Other less common but equally important indications may be diagnostic
        (fetoscopy, fetal tissue sampling, estimation of fetal haemoglobin) or
        therapeutic (aspiration of various fetal cavities, fetal blood
        transfusion and embryo reductions). In a high HIV prevalence setting
        like South Africa, a significant proportion of pregnant women in need
        of invasive procedures will be HIV-infected.

    

    
        There are no published data on the number of invasive procedures
        done in South Africa, but unpublished data from national laboratories
        suggest that the services are under-utilised.1 In
        2008, 6 out of 7 national laboratories received 529 amniocentesis
        specimens done for advanced maternal age – this in a background
        of 1 049 300 live births.1
        ,
        2
    

    
    

    In a high HIV prevalence setting like South Africa, where the
    estimated prevalence in antenatal clinic attendees was 29.4% in 2009, a
    significant proportion of pregnant women in need of invasive procedures
    will be HIV-infected.3 
    HIV clinicians need to be aware of the risk of mother-to-child
    transmission of HIV (MTCT) associated with invasive procedures, and
    should also be aware of strategies available to minimise the risk. This
    information needs to be given to clients during the counselling session
    before the procedure, and HIV clinicians may also be asked to advise
    obstetric colleagues on optimal management in cases where a
    HIV-infected woman requires a prenatal invasive procedure.

    TIMING OF INVASIVE PROCEDURES IN PREGNANCY

    Below is a list of commonly performed antenatal invasive obstetric
    procedures and the gestational age at which each procedure can, or
    should, be performed.

    n	Amniocentesis: from 16 weeks

    n	Chorionic villus sampling: from 11 to 14 weeks

    n	Cordocentesis: from 20 weeks

    n	Fetoscopy: usually in the 2nd and 3rd trimesters

    n	Fetal tissue sampling (biopsies of organs, muscle, etc.): usually in the 2nd and 3rd trimesters

    n	Aspiration of various fetal cavities, shunt insertion: any gestational age – usually from 16 weeks

    n	Embryo reductions: from 11 weeks.

    Several complications may occur with invasive procedures, and as
    part of pre-procedure counselling the woman/couple should be made aware
    of the risk of procedure-related complications. These include injury to
    maternal bowel, fetal injury, failure to obtain a sample,
    chorio-amnionitis, and most significantly fetal loss.4 
    The Royal College of Obstetricians and Gynaecologists guideline on
    amniocentesis and chorionic villus sampling advises that patients
    should be informed of an additional 1% risk of fetal loss following an
    amniocentesis, and a slightly higher risk following chorionic villus
    sampling.5 
    A 2003 Cochrane Review advises that, for second-trimester testing,
    amniocentesis is the safer procedure – safer than early
    amniocentesis or transcervical chorionic villus sampling.6  For testing before 15 weeks of pregnancy, transabdominal chorionic villus sampling is the safer procedure.6  There is no literature to suggest that the risk of procedure-related complications is higher in HIV-infected women.

    RISK OF MTCT WITH ANTENATAL INVASIVE PROCEDURES

    There is limited literature on invasive obstetric procedures in the
    context of maternal HIV infection. Few studies have been published on
    the topic, most with a small number of patients. Important risk factors
    for MTCT such as maternal HIV viral load and CD4+
    cell count are not always controlled for, and it may be difficult to
    infer causality in the reported cases of transmission after an invasive
    procedure. Without any maternal antiretroviral therapy initiated before
    an invasive procedure the risk of MTCT with invasive obstetric
    procedures is high, with rates of over 30% reported in some studies.7 
    In one study evaluating the effect of various factors on the risk on
    MTCT, third-trimester amniocentesis without any antiretroviral cover
    was associated with a fourfold increase in the risk of MTCT.8





With the use of combination antiretroviral therapy before antenatal
invasive procedures, the risk of MTCT is reported to be similar to that
of a HIV-infected pregnant woman who has not had an invasive procedure.9 
In studies reporting no MTCT with combination antiretroviral therapy, a
significant number of women were initiated on therapy before
conception, and the majority were virally suppressed at the time of the
procedure.9 
Despite the decrease in HIV transmission with antiretroviral cover,
procedures that require more technical skills – such as chorionic
villus sampling and cordocentesis – should still be avoided in
the HIV-infected woman, as the risk of transmission to the fetus may be
considerably increased. 




Guidelines on the techniques of performing invasive procedures
should be adhered to, and where possible the transplacental route
should be avoided owing to the higher risk of transmission.12


RECOMMENDATIONS ON ANTIRETROVIRAL PROPHYLAXIS PRIOR TO INVASIVE PROCEDURES

There is now general consensus that any HIV-infected pregnant woman
who needs to undergo an invasive obstetric procedure should have
combination antiretroviral therapy initiated before the procedure,
regardless of maternal CD4+ cell count.12
,
13 
Ideally, antiretroviral therapy should be initiated at least 4 - 6
weeks prior to the procedure to achieve a significant level of maternal
HIV viral suppression.14 
If the gestational age precludes waiting for the period of 4 - 6 weeks,
the clinician can still go ahead with the procedure as continuation of
combination antiretroviral therapy after the procedure
should provide post-exposure prophylaxis. There is, however, no
evidence on the role of post-procedure combination antiretroviral
therapy as post-exposure prophylaxis, but an analogy between needling
procedures and needle-stick injuries has been made. 




There are no data available to suggest a viral load
at which HIV transmission is unlikely to occur with an antenatal
invasive procedure, and data from general MTCT studies cannot be
extrapolated to cases with invasive procedures. However, both the Royal
College of Obstetricians and Gynaecologists and the British HIV
Association recommend an undetectable maternal viral load at the time
of the invasive procedure.12
,
13 
If resources allow and there is sufficient time to wait before the
invasive procedure, the maternal viral load should be determined as
part of pre-procedure counselling.




In a high HIV prevalence setting like South Africa,
it is advisable that a repeat HIV test be offered immediately before
the invasive procedure if a woman has initially tested HIV-negative
early in pregnancy.




Although there are no well-established approaches for
managing HIV-infected women undergoing invasive procedures,
international guidelines and literature published on the topic do offer
guidance for the clinician. Local guidelines that are in line with
international best practices, but also account for the nature of
HIV/AIDS and obstetric practice in South Africa, are required to guide
local clinicians. 




REFERENCES 

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Effectiveness of prenatal screening for Down syndrome on the basis of
maternal age in Cape Town. S Afr Med J 2011;101:45-48.

1. Urban MF, Stewart C, Ruppelt T, et al.
Effectiveness of prenatal screening for Down syndrome on the basis of
maternal age in Cape Town. S Afr Med J 2011;101:45-48.

2.	Statistics South Africa. Mid-year Population Estimates, 2009. Pretoria: Statistics South Africa, 2009.

2.	Statistics South Africa. Mid-year Population Estimates, 2009. Pretoria: Statistics South Africa, 2009.

3. Department of Health. National Antenatal Sentinel
HIV and Syphilis Prevalence Survey in South Africa, 2009. Pretoria:
Department of Health, 2010.

3. Department of Health. National Antenatal Sentinel
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