Antiretroviral Therapy During Pregnancy and Premature Birth
Background There is an ongoing debate as to whether combined antiretroviral treatment (cART) during pregnancy is an independent risk factor for prematurity in HIV-1-infected women.
Objective The aim of the study was to examine (1) crude effects of different ART regimens on prematurity, (2) the association between duration of cART and duration of pregnancy, and (3) the role of possibly confounding risk factors for prematurity.
Method We analysed data from 1180 pregnancies prospectively collected by the Swiss Mother and Child HIV Cohort Study (MoCHiV) and the Swiss HIV Cohort Study (SHCS).
Results Odds ratios for prematurity in women receiving mono/dual therapy and cART were 1.8 [95% confidence interval (CI) 0.85–3.6] and 2.5 (95% CI 1.4–4.3) compared with women not receiving ART during pregnancy (P=0.004). In a subgroup of 365 pregnancies with comprehensive information on maternal clinical, demographic and lifestyle characteristics, there was no indication that maternal viral load, age, ethnicity or history of injecting drug use affected prematurity rates associated with the use of cART. Duration of cART before delivery was also not associated with duration of pregnancy.
Conclusion Our study indicates that confounding by maternal risk factors or duration of cART exposure is not a likely explanation for the effects of ART on prematurity in HIV-1-infected women.
There is an ongoing debate as to whether or not the use of combined antiretroviral therapy (cART) in pregnant women increases the risk of prematurity. An association between use of cART and preterm delivery was initially reported by the Swiss Mother and Child HIV Cohort Study (MoCHiV) in 1998 and subsequently confirmed by the European Collaborative Study (ECS) and the MoCHiV. Based on an analysis of nearly 4000 mother–child pairs, and controlling for maternal CD4 cell count and injecting drug use (IDU), a two- to threefold increase in prematurity for neonates of mothers treated with cART as compared with no ART or exclusive exposure to zidovudine (ZDV) mono-prophylaxis during pregnancy was found. Furthermore, starting cART before pregnancy as compared with starting in the third trimester was associated with a twofold increase in the prematurity risk. In contrast, Tuomala et al. found similar rates of premature delivery of 16 and 17% among women who received ART and those who did not. cART was not associated with a higher prematurity rate or lower birth weights as compared with no ART or monotherapy during pregnancy. Their analysis was based on over 3000 mother–child pairs enrolled between 1990 and 1998 in seven clinical studies in the USA. In addition to maternal CD4 cell count, they were able to adjust premature birth rates in relation to cART exposure during pregnancy for the use of tobacco, alcohol and illicit drugs.
To explain the discrepancy between studies in the relationship between cART exposure during pregnancy and rate of premature birth, Tuomala et al. suggested confounding by other specific risk factors for prematurity in the ECS and MoCHiV analysis. The combined ECS and MoCHiV analysis was only controlled for maternal CD4 cell count, IDU and maternal age, while information on other potential confounders was simply not available. For the Swiss pregnancy data included in the study this situation has changed following the full integration of MoCHiV into the adult Swiss HIV Cohort Study (SHCS). Following successful linkage of MoCHiV mother identifications (IDs) to SHCS patient IDs, additional maternal data, including comprehensive information on treatment history and demographic and lifestyle characteristics, became available for a substantial number of mothers. The updated information also allowed us to control for changes in the potency of ART regimens prior to and during pregnancy as well as alterations in clinical, demographic and lifestyle characteristics of mothers over the past 20 to 25 years.
The main goal of the present study was to reassess the relationship between ART regimen (no ART, mono/dual ART or cART) used prior to and during pregnancy and the risk of premature birth. With respect to cART exposure, we particularly controlled for potential confounding by several maternal characteristics or risk factors during pregnancy, including lowest CD4 cell count during pregnancy, last HIV RNA load before delivery, age at conception, ethnicity, illicit drug use and smoking. We further investigated the association between the duration of cART before delivery and the duration of pregnancy.
Abstract and Introduction
Abstract
Background There is an ongoing debate as to whether combined antiretroviral treatment (cART) during pregnancy is an independent risk factor for prematurity in HIV-1-infected women.
Objective The aim of the study was to examine (1) crude effects of different ART regimens on prematurity, (2) the association between duration of cART and duration of pregnancy, and (3) the role of possibly confounding risk factors for prematurity.
Method We analysed data from 1180 pregnancies prospectively collected by the Swiss Mother and Child HIV Cohort Study (MoCHiV) and the Swiss HIV Cohort Study (SHCS).
Results Odds ratios for prematurity in women receiving mono/dual therapy and cART were 1.8 [95% confidence interval (CI) 0.85–3.6] and 2.5 (95% CI 1.4–4.3) compared with women not receiving ART during pregnancy (P=0.004). In a subgroup of 365 pregnancies with comprehensive information on maternal clinical, demographic and lifestyle characteristics, there was no indication that maternal viral load, age, ethnicity or history of injecting drug use affected prematurity rates associated with the use of cART. Duration of cART before delivery was also not associated with duration of pregnancy.
Conclusion Our study indicates that confounding by maternal risk factors or duration of cART exposure is not a likely explanation for the effects of ART on prematurity in HIV-1-infected women.
Introduction
There is an ongoing debate as to whether or not the use of combined antiretroviral therapy (cART) in pregnant women increases the risk of prematurity. An association between use of cART and preterm delivery was initially reported by the Swiss Mother and Child HIV Cohort Study (MoCHiV) in 1998 and subsequently confirmed by the European Collaborative Study (ECS) and the MoCHiV. Based on an analysis of nearly 4000 mother–child pairs, and controlling for maternal CD4 cell count and injecting drug use (IDU), a two- to threefold increase in prematurity for neonates of mothers treated with cART as compared with no ART or exclusive exposure to zidovudine (ZDV) mono-prophylaxis during pregnancy was found. Furthermore, starting cART before pregnancy as compared with starting in the third trimester was associated with a twofold increase in the prematurity risk. In contrast, Tuomala et al. found similar rates of premature delivery of 16 and 17% among women who received ART and those who did not. cART was not associated with a higher prematurity rate or lower birth weights as compared with no ART or monotherapy during pregnancy. Their analysis was based on over 3000 mother–child pairs enrolled between 1990 and 1998 in seven clinical studies in the USA. In addition to maternal CD4 cell count, they were able to adjust premature birth rates in relation to cART exposure during pregnancy for the use of tobacco, alcohol and illicit drugs.
To explain the discrepancy between studies in the relationship between cART exposure during pregnancy and rate of premature birth, Tuomala et al. suggested confounding by other specific risk factors for prematurity in the ECS and MoCHiV analysis. The combined ECS and MoCHiV analysis was only controlled for maternal CD4 cell count, IDU and maternal age, while information on other potential confounders was simply not available. For the Swiss pregnancy data included in the study this situation has changed following the full integration of MoCHiV into the adult Swiss HIV Cohort Study (SHCS). Following successful linkage of MoCHiV mother identifications (IDs) to SHCS patient IDs, additional maternal data, including comprehensive information on treatment history and demographic and lifestyle characteristics, became available for a substantial number of mothers. The updated information also allowed us to control for changes in the potency of ART regimens prior to and during pregnancy as well as alterations in clinical, demographic and lifestyle characteristics of mothers over the past 20 to 25 years.
The main goal of the present study was to reassess the relationship between ART regimen (no ART, mono/dual ART or cART) used prior to and during pregnancy and the risk of premature birth. With respect to cART exposure, we particularly controlled for potential confounding by several maternal characteristics or risk factors during pregnancy, including lowest CD4 cell count during pregnancy, last HIV RNA load before delivery, age at conception, ethnicity, illicit drug use and smoking. We further investigated the association between the duration of cART before delivery and the duration of pregnancy.
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