Is Antiretroviral Therapy during Pregnancy Associated with an Increased Risk of Preterm Delivery, Low Birth Weight, or Stillbirth?

Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, University of Miami, Miami, Florida 33101, USA.
The Journal of Infectious Diseases (Impact Factor: 6). 06/2006; 193(9):1195-201. DOI: 10.1086/503045
Source: PubMed

ABSTRACT Data on complications of pregnancy associated with antiretroviral therapy are limited. Some small studies have demonstrated an increased preterm delivery rate, but a recent retrospective United States multisite study did not concur with these findings. Our objective was to investigate whether antiretroviral therapy was associated with adverse pregnancy outcome at a single site.
Using prospectively gathered data, women were identified who were determined to be human immunodeficiency virus positive before or during pregnancy who sought care at our prenatal clinic and who gave birth at the University of Miami/Jackson Memorial Medical Center from 1990 through 2002. The outcome measures were preterm delivery, low birth weight, and stillbirth.
The cohort included 999 women who received antiretroviral therapy during pregnancy (monotherapy in 492, combination therapy without a protease inhibitor [PI] in 373, and combination therapy with a PI in 134) and 338 women who did not receive therapy. After adjustment for possible confounders, only combination therapy with a PI was associated with an increased risk of preterm delivery, compared with any other combination (odds ratio, 1.8 [95% confidence interval, 1.1-3.0]). There were no differences in rates of low birth weight and stillbirth, regardless of therapy.
Compared with monotherapy and combination therapy without a PI, only combination therapy with a PI was associated with an increased risk of preterm delivery.

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    • "Although numerous studies have addressed the question of a potential association between PI-based HAART and preterm birth, it remains controversial. Since the first European study brought this issue to light in 2000, several others, emphasizing the role of PIs and early onset of therapy, have confirmed the risk.38–40 It has been hypothesized that the physiopathology of preterm birth in the context of PI-based HAART involves immune reconstitution with cytokine shifts that induce the premature onset of labor, rather than any fetal or uteroplacental cause.41,42 "
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    ABSTRACT: The dire conditions of the human immunodeficiency virus/acquired immune deficiency syndrome epidemic and the immense benefits of antiretroviral prophylaxis in prevention of mother-to-child transmission far outweigh the potential for adverse effects and undeniably justify the rapid and widespread use of this therapy, despite incomplete safety data. Highly active antiretroviral therapy has now become standard care, and more than half the validated regimens include protease inhibitors. This paper reviews current knowledge of the safety of these drugs during pregnancy, in terms of maternal and fetal outcomes. Transfer of protease inhibitors across the placenta is known to be minimal, and current data about birth defects and fetal malignancies are reassuring. Maternal liver function and glucose metabolism should be monitored in women treated with protease inhibitor-based regimens, but concerns about the development of maternal resistance, should treatment be discontinued, have been shown to be groundless. Neonates should be screened for hematologic abnormalities, although these are rarely severe or permanent and are not usually related to the protease inhibitor component of the antiretroviral combination. Current findings concerning pre-eclampsia and growth restriction are discordant, and further research is needed to address the question of placental vascular complications. The increased risk of preterm birth attributed to protease inhibitors should be interpreted with caution considering the discrepant results and the multitude of confounding factors often overlooked. Although data are thus far reassuring, further research is needed to shed light on unresolved controversies about the safety of protease inhibitors during pregnancy.
    HIV/AIDS - Research and Palliative Care 09/2013; 5:253-262. DOI:10.2147/HIV.S33058
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    • "After adjustment for possible confounders including disease severity, only combination therapy with a PI was associated with risk for preterm delivery compared to any other regimen (95% CI, 1.1–3.0) [16]. However, those receiving PIs had more advanced disease in this cohort. "
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    ABSTRACT: To determine rate and factors associated with small-for-gestational-age (SGA) births to women with HIV. Prospective data were collected from 183 pregnant women with HIV in an urban HIV prenatal clinic, 2000-2011. An SGA birth was defined as less than the 10th or 3rd percentile of birth weight distribution based upon cut points developed using national vital record data. Bivariate analysis utilized chi-squared and t-tests, and multiple logistic regression analyses were used. The prevalence of SGA was 31.2% at the 10th and 12.6% at the 3rd percentile. SGA at the 10th (OR 2.77; 95% CI, 1.28-5.97) and 3rd (OR 3.64; 95% CI, 1.12-11.76) percentiles was associated with cigarette smoking. Women with CD4 count>200 cells/mm3 at the first prenatal visit were less likely to have an SGA birth at the 3rd percentile (OR 0.29; 95% CI, 0.10-0.86). Women taking NNRTI were less likely to have an SGA infant at the 10th (OR 0.28; 95% CI, 0.10-0.75) and 3rd (OR 0.16; 95% CI, 0.03-0.91) percentiles compared to those women on PIs. In this cohort with high rates of SGA, severity of HIV disease, not ART, was associated with SGA births after adjusting for sociodemographic, medication, and disease severity.
    Infectious Diseases in Obstetrics and Gynecology 06/2012; 2012(1):135030. DOI:10.1155/2012/135030
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    • "The current prevention of mother-to-child transmission (PMTCT) guidelines in South Africa recommend zidovudine (AZT) from 14 weeks of pregnancy, single-dose nevirapine, 3-hourly AZT intrapartum and a single dose of tenofovir and emtracitabine post-partum, for women not eligible for lifelong antiretroviral treatment and antiretroviral treatment for those eligible starting as soon as possible in pregnancy (Department of Health, 2010a, b). Several studies in Europe and the USA have reported an increased risk of preterm delivery with antenatal highly active antiretroviral therapy (HAART), with associations of between 1.5- and 3.5-fold increased risk (Thorne et al., 2004; Cotter et al., 2006; Townsend et al., 2010a,b) and there are also preliminary indications from studies in sub-Saharan Africa (SSA) of the same association (Powis et al., 2011; van der Merwe et al., 2011). This has been hypothesized to be due to an immunological mechanism, with HAART in pregnancy associated with a reversal of the Th1 to Th2 switch that is an immunological feature of normal pregnancy (Fiore et al., 2006) rather than being caused by infant or placental factors. "
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    ABSTRACT: BACKGROUND Human immunodeficiency virus (HIV) is prevalent in many countries where small-for-gestational age (SGA) and premature delivery are also common. However, the associations between maternal HIV, preterm delivery and SGA infants remain unclear. We estimate the prevalence of SGA and preterm (<37 weeks) births, their associations with antenatal maternal HIV infection and their contribution to infant mortality, in a high HIV prevalent, rural area in South Africa. METHODS Data were collected, in a non-randomized intervention cohort study, on all women attending antenatal clinics (2001–2004), before the availability of antiretroviral treatment. Newborns were weighed and gestational age was determined (based on last menstrual period plus midwife assessment antenatally). Poisson regression with robust variance assessed risk factors for preterm and SGA birth, while Cox regression assessed infant mortality and associated factors. RESULTS Of 2368 live born singletons, 16.6% were SGA and 21.4% were preterm. HIV-infected women (n= 1189) more commonly had SGA infants than uninfected women (18.1 versus 15.1%; P = 0.051), but percentages preterm were similar (21.8 versus 20.9%; P = 0.621). After adjustment for water source, delivery place, parity and maternal height, the SGA risk in HIV-infected women was higher [adjusted relative risk (aRR) 1.28, 95% confidence interval (CI): 1.06–1.53], but the association between maternal HIV infection and preterm delivery remained weak and not significant (aRR: 1.07, 95% CI: 0.91–1.26). In multivariable analyses, mortality under 1 year of age was significantly higher in SGA and severely SGA than in appropriate-for-gestational-age infants [adjusted hazard ratio (aHR): 2.12, 95% CI: 1.18–3.81 and 2.77, 95% CI: 1.56–4.91], but no difference in infant mortality was observed between the preterm and term infants (aHR: 1.18 95% CI: 0.79–1.79 for 34–36 weeks and 1.31, 95% CI: 0.58–2.94 for <34 weeks). CONCLUSIONS Maternal HIV infection increases the risk of SGA, but not preterm births, in this cohort.
    Human Reproduction 03/2012; 27(6):1846-56. DOI:10.1093/humrep/des090 · 4.57 Impact Factor
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