Page 371 - SAHCS HIVMed Journal Vol 20 No 1 2019

Page 10 of 12 Original Research

will generate adequate first-trimester NVP exposures to Conclusion
further explore this association. Previous international
reports have not found an association between NVP-based We found no association between first-trimester exposure to
ART exposure and the risk of CMs but with other ABOs such EFV-based treatments and risk of congenital malformations.
as stillbirths. 16,36,37 The risk of other ABOs is greater among HIV-exposed
versus HIV-unexposed infants. However, the timing of
Data on early exposure to TDF, FTC and EFV will dominate initiation of EFV and NVP-based ART regimens, in relation
future analyses, facilitating improved quantification of risks to conception, did not affect the risk of ABOs. While
of ABOs. Similarly, information on the safety of second-line reassuring, the data are not yet sufficient to completely
regimens will grow. The recent safety signal of an association exclude relevant drug-related risks associated with the
between dolutegravir-based ART and the risk of neural tube components of the current first-line ART regimen for
defects in Botswana is already delaying the use of this pregnant women in South Africa, and surveillance should
effective regimen in women with child-bearing potential. be continued. The unexpected statistically significant
This has highlighted the importance of ongoing pregnancy associations, found between T1 exposure to NVP and CMs,
exposure surveillance in African settings where the burden of demonstrate the need to continue to monitor the safety of
HIV and other communicable diseases is high, given a medicines in pregnancy even in the absence of previous
growing pipeline of new medicines, including vaccines, animal and human evidence of teratogenic risk. These
targeting pregnant women. initial signals of statistical association need to be reassessed
using multivariable analysis as the surveillance system
The conservative inclusion of only cases with a definite expands. The overall low rate of CMs in women on the
timing of exposure into the risk factor analysis meant that a current first-line ART regimen (TDF/FTC/EFV) for
significant proportion (30.4%) of the cohort of ART-exposed pregnant women in South Africa is reassuring and
birth outcomes were excluded from the analyses. However, supported by similar work in Botswana. 12,16,17,38
we found no difference between the cohort that was
included in the risk analysis and the excluded group in This PER/BDS surveillance system, having produced
terms of age category, parity and educational status, and significant unexpected, albeit crude, associations in its first
believe that the exclusion of these cases is unlikely to bias year, is clearly creating a rich resource of data. This will be
our findings. As the surveillance system matures, we also critical for monitoring potential risk, for mothers and their
expect improved data on ART exposures from record infants, for widely used medicines and for addressing
linkage between maternal and child health services and the potential concerns with formal measures of low risks.
data captured in the national electronic ART registration
system (Tier.Net). Reported LMP dates will be augmented Acknowledgements
with data on gestational age from routine early ultrasound
scans to better characterise the timing of exposures. The cooperation of the women who provided information
Nevertheless, the low rates of SGA and PTD reported in this after delivery and the efforts of the surveillance nurses, data
study suggest that the estimations of gestational age at birth capturers and hospital staff who continue to work on this
may not be accurate. This can be attributed to the low novel surveillance project is gratefully acknowledged. Louisa
reporting of LMP, late presentation of prenatal ultrasound Bhengu, Engela Honey and Thirona Naicker served as
and lack of a standardised assessment used for assessing members of the CM review panel. Dr Augustin Ntilivamunda
prematurity at birth in labour ward. In future analyses, low and Dr Francois Renaud from WHO provided technical and
birth weight, albeit crude, may be a more reliable endpoint administrative support throughout the project.
to measure instead of SGA and PTD.
Competing interests
The background rates of common malformations detectable The authors have no conflict of interests.
at birth will be more reliably observed as capacity
development activities at this sentinel surveillance site are
expanded, including systematic assessment of stillbirths Authors’ contributions
and improved access to clinical genetic expertise at the site All listed authors contributed to the drafting and/or editing
for better characterisation and diagnosis of CMs detected of this manuscript. U.C.M. developed the protocol and
at the time of birth. The surveillance system is currently procedures, provided technical oversight throughout
only able to detect external visible malformations detectable the development of the surveillance system, developed the
immediately after delivery. As the surveillance system analysis plan together with C.v.S. and A.W. and drafted
matures and the ABOs under scrutiny accumulate, the report in collaboration and consultation with all
multivariable analyses incorporating the data collected on co-authors. C.v.S. assisted in data cleaning and conducted
other risk factors and exposures, including the use of the statistical analysis of the data. O.M. served as the
herbal and traditional medicines, illicit drugs, tobacco and chairperson of the project steering committee, N.R.M. and
alcohol, can be incorporated into the risk analyses as can N.N. provided clinical support for surveillance staff at the
calendar time. facilities. A.R. and P.N. were responsible for obtaining

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