Page 363 - SAHCS HIVMed Journal Vol 20 No 1 2019

Page 2 of 12 Original Research

7,8
5,6
delivery (PTD), low birth weight (LBW), small for with confirmed exposure to specific antiretroviral regimens.
gestational age (SGA), 9,10 stillbirth (SB), neonatal death Two separate analyses were conducted for CM (where the
9,11
(NND) and, according to some reports, congenital risk of teratogenic exposure is highest in the first trimester
9,11
malformations (CM). 12,13,14 In most of these situations, the when organogenesis occurs) and for other ABOs where the
contribution of the underlying HIV infection and other risk period of exposure is less well defined and more likely to
15
maternal risk factors is difficult to rule out. Further studies be continuous.
have investigated the relative safety of different ART
regimens, 16,17 while others have assessed whether the timing Methods
of the initiation of ART, in relation to conception, influences Setting
the risk of ABOs. 6,7,8,18
The birth defect (referred to as ‘congenital malformations’
Questions persist about the risk of ABOs associated with [CM] in this article) surveillance was carried out at Prince
exposure to specific antiretrovirals such as nevirapine (NVP) Mshiyeni Memorial Hospital (PMMH) in the KwaZulu-Natal
and protease inhibitors (PIs). 16,19 Most recently, concerns province of South Africa, where approximately 14 000
about the safety in pregnancy of dolutegravir (DTG), a long- deliveries occur each year. HIV prevalence among pregnant
anticipated agent with an improved efficacy and safety women in this province at the time of the study was steadily
profile, have been raised by early signals of higher rates of increasing from approximately 37.4% (95% CI 35.8% – 39.0%)
28
neural tube defects in infants exposed in utero at the time of in 2011 to 44.4% (95% CI 42.5% – 46.3%) in 2015, with
conception compared to efavirenz (EFV). 12 antenatal ART initiation rates increasing from 85.4% in
2013 and 2014 to 97.2% in 2015 and 2016. 29
A robust meta-analysis of data from the outcomes of 2026 live
births of women exposed to EFV during the first trimester Surveillance method
found only one case of a neural tube defect, and the rate of Five surveillance nurses surveyed the hospital’s maternity
CM was not higher than in infants exposed to non-EFV-
containing first-trimester regimens. In preclinical primate wards and labour ward registers to identify women who had
20
and clinical studies, in utero exposure to tenofovir (TDF) has recently delivered. The surveillance nurses collected
been associated with growth restriction, bone mineral content information on demographics, health and health-seeking
reduction and bone toxicity. 21,22 However, the Antiretroviral behaviour during pregnancy, obstetric and neonatal history,
Pregnancy Registry (APR), based in the United States, HIV status, medical conditions, medicine use including
concluded that a doubling and 1.5-fold increase in risk of folate, calcium and iron supplementation, and labour/
CMs, with EFV and TDF, respectively, could be ruled out delivery information. As they only worked from Monday to
based on the American background CM rate of 2.7%. Friday during office hours, there was incomplete coverage of
23
Similarly, no increase in the risk of CM has been observed deliveries during this initial pilot period. The women’s
with NVP to date. 24 maternity case records (MCRs) were used to confirm and
expand on what was reported during a brief interview. A
Given the relative rarity of CMs, lack of available data on systematic neonatal surface examination, recommended by
baseline rates of CM from low- and middle-income countries the WHO, was performed on all live infants and stillbirths
30
and the great number of exposures in HIV-affected settings (whenever feasible) by the trained surveillance nurses. Birth
like South Africa, Ford and others have recommended weight, length, head circumference and reported gestational
ongoing prospective birth outcomes surveillance. 20,25,26,27 age at birth were collected from the MCR. Gestational age at
Concerns about the safety of ART in the unborn child, birth is routinely documented by nursing staff based on the
applicable to millions of women who are and will be estimated date of delivery calculated during antenatal care
receiving ART during pregnancy in the coming years, will based on the last menstrual period (LMP) reported at the first
persist in the absence of controlled studies that are able to antenatal visit, and confirmed by ultrasound, when available.
quantify the risk of potential CMs and other ABOs such as Major CMs identified at birth were recorded on the
LBW, PTD, NND, SB and SGA. Hence, in 2013, the South surveillance system’s case record form. In the case of infants
African NDoH implemented a pregnancy exposure registry in the nursery who were premature, febrile, ill, or too fragile
(PER) and birth defect surveillance (BDS) system at selected to be unnecessarily handled, the surveillance nurses did not
sentinel sites to assess the association of medicines physically examine the infant themselves but rather referred
commonly used in pregnant women, initially focusing on to the clinical notes to complete the form.
antiretrovirals, with ABOs. In partnership with the
KwaZulu-Natal (KZN) Provincial Department of Health In the case of major CMs, digital photographs were taken if
and other supporting partners, the project was launched on consent was obtained from the mother. A CM confirmation
07 October 2013. form was completed and signed by a neonatologist or senior
clinician in the nursery ward designated to support the
We describe the findings of the first 12 months of this project, surveillance system. A CM review panel comprising medical
focusing on the risk of CM at birth and other ABOs (pregnancy geneticists, paediatricians and neonatologists confirmed
losses, NND, SGA, PTD and LBW) in infants born to mothers diagnoses of CMs by viewing photographs, the results of any

http://www.sajhivmed.org.za 356 Open Access