Miscarriage and stillbirth risk increases in smokers with HIV

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Smoking ‘dramatically’ increases the risk of pregnancy loss in HIV-positive women, US investigators report.

Researchers from the large Women’s Interagency HIV Study (WIHS) examined the impact of smoking on pregnancy loss in HIV-positive and HIV-negative women over a 20-year period. The effect of smoking on pregnancy loss differed dramatically by HIV status, increasing the absolute risk by 19% in HIV-positive women compared to 10% in HIV-positive women.

“We found strong evidence that current smoking at the visit prior to pregnancy increased risk of pregnancy loss in both HIV-positive and HIV-negative women,” comment the researchers. “We also found that the effect of smoking was substantially stronger among HIV-positive women, a finding robust in sensitivity analysis.”

Cigarette smoking during pregnancy increases the risk of pregnancy loss, a recent meta-analysis found. It showed that the risk of miscarriage is approximately a third higher among smokers compared to non-smokers. An estimated 35% of HIV-positive women in the US smoke, twice the rate seen in the general population. Both HIV and smoking are associated with inflammation and immune activation, processes associated with poor pregnancy outcomes. However, it is unclear if HIV and smoking interact to increase the risk of pregnancy loss.

Investigators at the University of North Carolina at Chapel Hill’s Gillings School of Global Public Health therefore examined the effect of smoking on the risk of pregnancy loss, comparing the differences in the effects between HIV-positive and HIV-negative women. Results were controlled to take account of potential confounders including age, race, BMI, employment status, income and drug and alcohol use.

The study population consisted of 659 women and 1,033 pregnancy outcomes. A total of 396 women were HIV-positive; these women had 592 pregnancies. Analysis of women with HIV showed that smokers had lower rates of antiretroviral therapy use (67% vs 80%), viral suppression (48% vs 71%) and lower CD4 cell counts (415 vs 485 cells/mm3) compared to non-smokers. HIV-positive smokers were also less likely than HIV-positive non-smokers to be employed and on a low income, but more likely to report use of injecting and non-injecting drugs and cannabis smoking.

Approximately a third of all pregnancies resulted in pregnancy loss, including 314 miscarriages and 12 stillbirths. After taking into account potential confounders, current smokers were 15% more likely to experience pregnancy loss compared to non-smokers.

The overall risk of pregnancy loss was similar for HIV-positive (33%) and HIV-negative (30%) women. In non-smokers, rates of pregnancy loss were similar for HIV-positive and HIV-negative women (22% vs 25%, respectively).

However, analysis of current smokers showed that 52% of pregnancies involving HIV-positive women resulted in pregnancy loss, compared to a rate of 33% in HIV-negative women.

Risk differences comparing smokers and non-smokers showed a greater effect in HIV-positive women compared to HIV-negative women (19% vs 10%, respectively).

Somewhat surprisingly, HIV-positive smokers on antiretroviral therapy and with viral suppression had a higher risk of pregnancy loss compared to HIV-positive people who were not taking HIV medication and who did not have viral suppression (24%, 22.5% vs 13%, 13%).

The investigators calculated that smoking increased the risk of pregnancy loss in HIV-negative women by approximately one third (aRR = 1.31; 95% CL 099-1.75) but by almost three-quarters in HIV-positive women (aRR = 1.74; 95% CL 1.36-2.23).

The findings remained robust in sensitivity analyses.

“One possible explanation for the strong effect of smoking on pregnancy loss risk among HIV-positive women is synergism due to inflammation, which is characteristic of both smoking and long-term HIV infection, although other results complicate this explanation,” write the investigators. “The lack of clear mechanism by which smoking apparently dramatically increases risk of pregnancy loss points towards future areas of research.”

The investigators estimated that it would be necessary to offer a well-designed smoking cessation intervention to 36 women to prevent one pregnancy loss. “We found that smoking is associated with large absolute increases in risk of pregnancy loss, that increases in risk are substantially larger among HIV-positive than HIV-negative women, and that realistic interventions can potentially lead to reduced incidence of pregnancy loss,” conclude the authors.

“Taken in concert with evidence from HIV-negative populations, this suggests that HIV-positive women planning a pregnancy should be strongly encouraged to cease smoking and supported in their efforts to do so, for their own health and to increase the probability of live birth.”

Objective: Cigarette smoking during pregnancy increases risks of poor pregnancy outcomes including miscarriage and stillbirth (pregnancy loss), but the effect of smoking on pregnancy loss among HIV-infected women has not been explored. Here, investigated the impact of smoking on risk of pregnancy loss among HIV-positive and HIV-negative women, and estimated the potential impact of realistic smoking cessation interventions on risk of pregnancy loss among HIV-positive women.
Design: We analyzed pregnancy outcomes in HIV-positive and HIV-negative participants in the Women’s Interagency HIV Study (WIHS) between 1994 and 2014.
Methods: We estimated effects of current smoking at or immediately before pregnancy on pregnancy loss; we controlled for confounding using regression approaches, and estimated potential impact of realistic smoking cessation interventions using a semi-parametric g-formula approach.
Results: Analysis examined 1033 pregnancies among 659 women. The effect of smoking on pregnancy loss differed dramatically by HIV status: adjusted for confounding, the risk difference comparing current smokers to current non-smokers was 19.2% (95% CL 10.9, 27.5%) in HIV-positive women and 9.7% (95% CL 0.0, 19.4%) in HIV-negative women. These results were robust to sensitivity analyses. We estimated that we would need to offer a realistic smoking cessation intervention to 36 women to prevent one pregnancy loss.
Conclusions: Smoking is a highly prevalent exposure with important consequences for pregnancy in HIV-positive pregnant women in the United States, even in the presence of potent highly active antiretroviral therapy. This evidence supports greater efforts to promote smoking cessation interventions among HIV-positive women, especially those who desire to become pregnant.

Westreich, Daniel; Cates, Jordan; Cohen, Mardge; Weber, Kathleen M; Seidman, Dominika; Cropsey, Karen; Wright, Rodney; Milam, Joel; Young, Mary A; Mehta, C Christina; Gustafson, Deborah R; Fischl, Margaret A; Adimora, Adaora A

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