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Elevated frequencies of micronucleated erythrocytes in infants exposed to zidovudine in utero and postpartum to prevent mother‐to‐child transmission of HIV
Author(s) -
Witt Kristine L.,
Cunningham Coleen K.,
Patterson Kristine B.,
Kissling Grace E.,
Dertinger Stephen D.,
Livingston Elizabeth,
Bishop Jack B.
Publication year - 2007
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.20266
Subject(s) - zidovudine , medicine , cord blood , transplacental , obstetrics , pregnancy , gestation , in utero , fetus , physiology , pediatrics , immunology , human immunodeficiency virus (hiv) , viral disease , biology , genetics , placenta
Zidovudine‐based antiretroviral therapies (ARTs) for treatment of HIV‐infected pregnant women have markedly reduced mother‐to‐child transmission of the human immunodeficiency virus (HIV‐1) from ∼25% to <1%. However, zidovudine (ZDV; AZT), a nucleoside analogue, induces chromosomal damage, gene mutations, and cancer in animals following direct or transplacental exposure. To determine if chromosomal damage is induced by ZDV in infants exposed transplacentally, we evaluated micronucleated reticulocyte frequencies (%MN‐RET) in 16 HIV‐infected ART‐treated mother–infant pairs. Thirteen women received prenatal ART containing ZDV; three received ART without ZDV. All infants received ZDV for 6 weeks postpartum. Venous blood was obtained from women at delivery and from infants at 1–3 days, 4–6 weeks, and 4–6 months of life; cord blood was collected immediately after delivery. Ten cord blood samples (controls) were obtained from infants of HIV‐uninfected women who did not receive ART. %MN‐RET was measured using a single laser 3‐color flow cytometric system. Tenfold increases in %MN‐RET were seen in women and infants who received ZDV‐containing ART prenatally; no increases were detected in three women and infants who received prenatal ART without ZDV. Specifically, mean %MN‐RET in cord blood of ZDV‐exposed infants was 1.67 ± 0.34 compared with 0.16 ± 0.06 in non‐ZDV ART‐exposed infants ( P = 0.006) and 0.12 ± 0.02 in control cord bloods ( P < 0.0001). %MN‐RET in ZDV‐exposed newborns decreased over the first 6 months of life to levels comparable to cord blood controls. These results demonstrate that transplacentalZDV exposure is genotoxic in humans. Long‐term monitoring of HIV‐uninfected ZDV‐exposed infants isrecommended to ensure their continued health. Environ. Mol. Mutagen. Published 2007 Wiley‐Liss, Inc.