infants born to mothers in Botswana and exposed during pregnancy to maternal
antiretroviral treatment were at increased risk for severe anaemia during the
first six months of life compared to infants exposed to short-term zidovudine
alone, Scott Dryden-Peterson and colleagues reported in an analysis of the
Mashi and Mma Bana PMTCT intervention trials published in
the advance online edition of the Journal
of Acquired Immune Deficiency Syndromes.
infants on short-term zidovudine had the lowest risk for anaemia.
decreased odds, compared to breastfed infants exposed to maternal ART and for those
exposed to short-term zidovudine, were 5.8 fold and 2.2 fold, respectively.
Observational studies of large cohorts in the United
States and Europe had
a separate report on infants born to mothers participating in the two trials Kathleen
M Powis and colleagues reported that while lower birth weight was associated
with infant exposure to maternal antiretroviral treatment compared to exposure
to short-term zidovudine, rapid weight gain within the first three months
brought the infants close to the norm for age and gender.
this is reassuring low birth weight nonetheless is associated with the
potential for early infant mortality and/or morbidity, note the authors.
findings were published in the February 1 edition of the Journal of Acquired Immune Deficiency Syndromes.
ART during pregnancy and breastfeeding for the prevention of mother-to-child
transmission is an effective public health intervention. The World Health
Organization (WHO) now recommends ART for all pregnant women with CD4 cell
counts of 350 cells/mm3or lower and as an MTCT prevention strategy
in women with higher CD4 cell counts. This is of particular relevance for women
in resource-poor settings where formula-feeding may be neither safe nor
it is important to look at the potential toxicity of infant exposure to
maternal ART during pregnancy, as well as the short- and long-term growth
implications for infants. Evidence is limited, especially in resource-poor
and other nucleoside reverse transcriptase inhibitors (NRTIs) are known to
cause anaemia in adults and children. Studies in resource-rich settings suggest
ART causes mild but reversible anaemia. However, in resource-poor settings
malnutrition and limited access to blood transfusions make the risk for, and
adverse effects of severe anaemia of critical clinical significance.
Dryden-Petersen and colleagues compared severe anaemia rates among three
groups: infants exposed to maternal ART during pregnancy, breastfeeding and one
month of postnatal zidovudine (ART-BF); infants exposed to maternal zidovudine
during pregnancy, six months of postnatal zidovudine and breastfeeding
(ZDV-BF); and infants exposed to maternal zidovudine during pregnancy, one
month of postnatal zidovudine and formula-feeding (ZDV-FF).
1719 infants severe anaemia was found in 7.4% (118). By six months 12.5% of the
ART-BF group had severe anaemia compared with 5.3% of the ZDV-BF group and
2.5%in the ZDV-FF group.
authors note the apparent contradiction between their findings and an earlier
analysis (Bae et al) is due to small sample size (178 compared to 1719
infants), inclusion of HIV-infected infants and most importantly use of the
1994 version of the DAIDS toxicity table. Exclusion of the HIV-infected infants
and use of the 2004 table in the Bae analysis gave similar results to their
authors suggest that timing of exposure to ART or the combination of zidovudine
with other antiretrovirals may help explain why those in the ART-BF group had
the most severe anaemia. A study in Malawi suggested exposure to ART
during pregnancy increased the risk for anaemia.
types of anaemia found corresponded to iron-deficiency. All mothers in both the
Mashi and Mma Bana studies were given iron supplements as part of antenatal
care. So ART may affect the absorption of iron from mother to foetus as well as
make the infant vulnerable because of nutrient deficiencies and infections,
include: most of the ART-exposed infants were breastfed so separation of
antiretroviral and feeding effects were not possible. There is no way of
knowing the effect of antenatal and postnatal ART exposure on anaemia.
authors note that while these limitations may underestimate the effect of
maternal ART on anaemia, conclusive causality between ART exposure during
pregnancy and infant anaemia was not found suggesting the need for further
anaemias were asymptomatic and improved with iron and vitamin supplements and
is unknown whether anaemia not caused by iron deficiency affects child
development. The authors note this warrants further study of the aetiology of
anaemia in ART-exposed infants.
M Powis and colleagues undertook the first study to compare early growth
patterns of breastfed infants after ART or zidovudine exposure during
patterns of 619 ART-exposed and 440 zidovudine-exposed HIV-uninfected infants
and zidovudine-exposed infants had mean birth weights (WAZ) of 3.01kg and 3.15
kg, p<0.01, respectively. All
ART-exposed infants had lower length for age (LAZ) and weight for length (WLZ)
scores at birth compare to zidovudine-exposed infants.
from birth until two months of age ART-exposed infants showed the greatest
improvements in weight for age and weight for length. And, from three to six
months of age there was no difference in weight for age between the groups.
the first 28 days of life a study from Tanzania showed that lower birth
weight among HIV-exposed infants presented a higher risk for death than HIV
transmission. The authors stress that infants exposed to maternal ART “may
benefit from programmes to optimise growth in the first several months of life
in an effort to mitigate morbidity and mortality.”
for age was lower in ART-exposed infants. The authors note Mma Bana infants
will be followed beyond six months allowing for a re-evaluation of morbidity
and mortality outcomes.
include the difference in protocols: zidovudine-exposed infants got zidovudine
throughout the six month breastfeeding period, while ART-exposed infants got
zidovudine for four weeks.
authors conclude “this analysis is the first to provide reassurance that lower
birth weight associated with in utero ART-exposed infants does not persist
during early infancy. It also highlights [as does the analysis by
Dryden-Peterson and colleagues] the importance of early and routinely scheduled
health care for ART-exposed HIV-uninfected infants.”