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Seroprevalence of antibodies to Chlamydia pneumoniae in women with preeclampsia
Andres Calle, MD, MSc Hospital Gineco-Obstetrico Isidro Ayora Quito, Ecuador
REFERENCE 1. Heine RP, Ness RB, Roberts JM. Seroprevalence of antibodies to Chlamydia pneumoniae in women with preeclampsia. Obstet Gynecol 2003;101:221–6.
In Reply: Our thanks to Teran et al for sharing their experience with serological testing for Chlamydia pneumoniae, Helicobacter pylori, and anti–streptolysin O among preeclamptic and control women. Although their results differ from ours, the divergence is not as great as it appears from their table. This is because their calculated odds ratios (ORs) reflect the risk of having a negative antibody titer rather than a positive one. Their OR for the proportion of preeclamptic women versus controls with a positive C pneumoniae titer is 1.8 (95% confidence interval [CI] 0.4, 9.1). That is, in the Teran et al study, evidence of previous C pneumoniae infection elevated the risk of preeclampsia almost two-fold. In comparison, the OR (95% CI) from our report was 3.1 (1.2, 7.9). That the CIs from the Teran et al study and ours overlap suggests that these estimates do not statistically differ. The modestly lower point estimate for C pneumoniae in the Teran et al study may be because the unusually high rate of preeclampsia (13.1%) or the extremely high rate of having a positive C pneumoniae titer among controls may reflect some misclassification. Investigation of the link between C pneumoniae and preeclampsia in larger epidemiological studies is warranted. Further, experimental work in animal models should be pursued to support the biologic plausibility of this relationship. The fact that Teran and colleagues’ result essentially replicates our own lends credence to the observation that an elevated C pneumoniae antibody titer is associated with preeclampsia. Roberta B. Ness, MD, MPH James M. Roberts, MD University of Pittsburgh and Magee-Womens Research Institute Pittsburgh, Pennsylvania Phillip R. Heine, MD Duke University Medical Center Durham, North Carolina
VOL. 102, NO. 1, JULY 2003
Screening Interval and Risk of Invasive Squamous Cell Cervical Cancer To the Editor: Miller et al1 examine a topic with important health and economic implications in their study of the risk of cervical cancer after Papanicolaou screening at different yearly intervals. They conclude that females screened at 1-year intervals are significantly less likely to develop cervical cancer than those screened every 2 or 3 years. I am concerned, however, that the methods are biased in several ways towards finding a benefit from more frequent screening. First, the authors do not examine the actual interval between two successive Papanicolaou smears, but rather the time from a normal previous smear to 1) the date of a cancer diagnosis among case subjects and 2) that same date for controls. This unconventional screening interval definition, on average, captures controls at the midpoint between a prior and subsequent smear. Thus, actual screening intervals for most controls should be substantially increased. Correctly reporting more controls with longer screening intervals would be expected to increase the cervical cancer risk at a 1-year screening interval and lower it at 2- and 3-year intervals, thereby diminishing the benefits of more frequent screening. Second, for cases, some intervals are biased in the opposite direction. Women sometimes have several repeat abnormal smears before a cervical cancer diagnosis. For instance, consider an actual Papanicolaou sequence of normal (1997), low-grade squamous intraepithelial lesion (1998), atypical squamous cells (1998), and a cancer diagnosis in 1999. The Miller study classifies this woman as having a 2-year screening interval, when it can be seen she was actually screened at a 1-year interval after her normal 1997 smear. This differential does not apply to most controls. The resulting bias is that the proportion of cases and the relative risk of cancer from screening at 2- to 3-year intervals are overestimated. The authors attempt to adjust for repeat screens by including “ever having had an abnormal smear” as a control variable. However, this does not eliminate the problem, as the abnormal smear is likely immediately before the cancer diagnosis for case subjects versus perhaps as far back as 20 –30 years for controls. For these reasons, I believe study designs using actual intervals between Papanicolaou smears are needed to draw conclusions concerning the merits of different screening intervals.
Letters
199
REFERENCE 1. Heine RP, Ness RB, Roberts JM. Seroprevalence of antibodies to Chlamydia pneumoniae in women with preeclampsia. Obstet Gynecol 2003;101:221–6.
In Reply: Our thanks to Teran et al for sharing their experience with serological testing for Chlamydia pneumoniae, Helicobacter pylori, and anti–streptolysin O among preeclamptic and control women. Although their results differ from ours, the divergence is not as great as it appears from their table. This is because their calculated odds ratios (ORs) reflect the risk of having a negative antibody titer rather than a positive one. Their OR for the proportion of preeclamptic women versus controls with a positive C pneumoniae titer is 1.8 (95% confidence interval [CI] 0.4, 9.1). That is, in the Teran et al study, evidence of previous C pneumoniae infection elevated the risk of preeclampsia almost two-fold. In comparison, the OR (95% CI) from our report was 3.1 (1.2, 7.9). That the CIs from the Teran et al study and ours overlap suggests that these estimates do not statistically differ. The modestly lower point estimate for C pneumoniae in the Teran et al study may be because the unusually high rate of preeclampsia (13.1%) or the extremely high rate of having a positive C pneumoniae titer among controls may reflect some misclassification. Investigation of the link between C pneumoniae and preeclampsia in larger epidemiological studies is warranted. Further, experimental work in animal models should be pursued to support the biologic plausibility of this relationship. The fact that Teran and colleagues’ result essentially replicates our own lends credence to the observation that an elevated C pneumoniae antibody titer is associated with preeclampsia. Roberta B. Ness, MD, MPH James M. Roberts, MD University of Pittsburgh and Magee-Womens Research Institute Pittsburgh, Pennsylvania Phillip R. Heine, MD Duke University Medical Center Durham, North Carolina
VOL. 102, NO. 1, JULY 2003
Screening Interval and Risk of Invasive Squamous Cell Cervical Cancer To the Editor: Miller et al1 examine a topic with important health and economic implications in their study of the risk of cervical cancer after Papanicolaou screening at different yearly intervals. They conclude that females screened at 1-year intervals are significantly less likely to develop cervical cancer than those screened every 2 or 3 years. I am concerned, however, that the methods are biased in several ways towards finding a benefit from more frequent screening. First, the authors do not examine the actual interval between two successive Papanicolaou smears, but rather the time from a normal previous smear to 1) the date of a cancer diagnosis among case subjects and 2) that same date for controls. This unconventional screening interval definition, on average, captures controls at the midpoint between a prior and subsequent smear. Thus, actual screening intervals for most controls should be substantially increased. Correctly reporting more controls with longer screening intervals would be expected to increase the cervical cancer risk at a 1-year screening interval and lower it at 2- and 3-year intervals, thereby diminishing the benefits of more frequent screening. Second, for cases, some intervals are biased in the opposite direction. Women sometimes have several repeat abnormal smears before a cervical cancer diagnosis. For instance, consider an actual Papanicolaou sequence of normal (1997), low-grade squamous intraepithelial lesion (1998), atypical squamous cells (1998), and a cancer diagnosis in 1999. The Miller study classifies this woman as having a 2-year screening interval, when it can be seen she was actually screened at a 1-year interval after her normal 1997 smear. This differential does not apply to most controls. The resulting bias is that the proportion of cases and the relative risk of cancer from screening at 2- to 3-year intervals are overestimated. The authors attempt to adjust for repeat screens by including “ever having had an abnormal smear” as a control variable. However, this does not eliminate the problem, as the abnormal smear is likely immediately before the cancer diagnosis for case subjects versus perhaps as far back as 20 –30 years for controls. For these reasons, I believe study designs using actual intervals between Papanicolaou smears are needed to draw conclusions concerning the merits of different screening intervals.
Letters
199