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Is caffeine use during pregnancy really unsafe?
Letters to the Editors
www.AJOG.org
Is caffeine use during pregnancy really unsafe? TO THE EDITORS: In the March 2008 issue of the Journal, the article by Weng et al suggested that “. . .it may be prudent to stop or reduce caffeine intake during pregnancy.”1 Although the authors state that their work overcomes the deficiencies of many previous studies looking at the impact of caffeine consumption on the risk of miscarriage, we respectfully disagree. In fact, their study suffers from many of the same problems that have plagued other work in this area. Although the authors repeatedly refer to their study as a prospective cohort study, reporting of caffeine consumption from LMP to interview was retrospective. Further, 59% of the women who miscarried were interviewed after their miscarriage, raising concerns of recall bias. Although the authors state in the Discussion that they performed a stratified analysis looking at the results among women who miscarried before the interview vs after and there were no differences, these data are quite important and should have been reported among the main results of the study. There is some confusion with regard to the selection of “confounders” included in the final models. Although variables such as Jacuzzi use and magnetic field exposure were available in the overall dataset, their relation to caffeine consumption and therefore status as true confounders in this analysis is unclear. We are particularly concerned about the inclusion of history of previous miscarriage as a confounder in the model; something that should have been addressed using more sophisticated techniques such as hierarchical modeling.2 We also question why the authors stratified by a change in caffeine intake during pregnancy and controlled for nausea and vomiting in the final adjusted models. There is a substantial body of literature that suggests that the presence of nausea and vomiting is indicative of a healthy pregnancy3; therefore, controlling for this factor may in effect be controlling for the very outcome being studied, rendering such control uninterpretable.
It is worth noting that Savitz et al4 recently published an article on this same topic. They found little evidence of an association between caffeine consumption before or early in pregnancy and the risk of miscarriage. Their study also involved retrospective reporting, with some of the interviews occurring after the miscarriage. Indeed, in stratifying the results by time of interview, they found evidence of positive associations among those women whose interview occurred after the loss, while there were no associations among those who were interviewed before the loss occurred. f Courtney D. Lynch, PhD, MPH Division of Epidemiology The Ohio State University College of Public Health B218 Starling-Loving Hall 320 W. 10th Ave. Columbus, OH 43210 [email protected] Mark A. Klebanoff, MD, MPH Germaine M. B. Louis, PhD, MS Epidemiology Branch Division of Epidemiology, Statistics and Prevention Research Eunice Kennedy Shriver National Institute of Child Health and Human Development Rockville, MD REFERENCES 1. Weng X, Odouli R, Li DK. Maternal caffeine consumption during pregnancy and the risk of miscarriage: a prospective cohort study. Am J Obstet Gynecol 2008;198:279.e1– e8. 2. Louis GB, Dukic V, Heagerty PJ, Louis TA, Lynch CD, Ryan LM, et al. Analysis of repeated pregnancy outcomes. Stat Methods Med Res 2006;5:103-26. 3. Weigel RM, Weigel MM. Nausea and vomiting of early pregnancy and pregnancy outcome: a meta-analytical review. Br J Obstet Gynaecol 1989;96:1312-8. 4. Savitz DA, Chan RL, Herring AH, Howards PP, Hartmann KE. Caffeine and miscarriage risk. Epidemiology 2008;19:55-62. © 2008 Mosby, Inc. All rights reserved. doi: 10.1016/j.ajog.2008.05.035
Oversight or Trompe l’oeil? TO THE EDITORS: Vercellini et al recently reported that the postoperative use of a low-dose oral contraceptive pill (OCP) reduces the risk of endometrioma recurrence.1 They retrospectively followed up on 277 patients who had undergone laparoscopic excision of ovarian endometriomas and who were offered OCP, and examined the recurrence rate in 3 groups: (1) patients who used OCP for the entire follow-up period (always users); (2) those who used OCP discontinuously (ever users); and (3) those who declined treatment (never users). By showing that group 3 has a significantly higher rate of recurrence than 1 group and 1 that, within group 2, patients used OCP for e16
American Journal of Obstetrics & Gynecology NOVEMBER 2008
ⱖ 12 months have a significantly lower recurrence rate than those who used less than 12 months, they concluded that the OCP used postoperatively is beneficial. Recognizing the possibility of a self-selection bias in patients, they argued that “women taking OCP could have been considered at higher risk of endometrioma recurrence because the suggestion to use postoperative medical treatment would be expected to be more probable after difficult or nonradical surgery than after routine procedures,”1 and hence their results could be conservative. However, a closer look at their presented data suggests that the selection bias is in the direction opposite to what the au-
www.AJOG.org
Is caffeine use during pregnancy really unsafe? TO THE EDITORS: In the March 2008 issue of the Journal, the article by Weng et al suggested that “. . .it may be prudent to stop or reduce caffeine intake during pregnancy.”1 Although the authors state that their work overcomes the deficiencies of many previous studies looking at the impact of caffeine consumption on the risk of miscarriage, we respectfully disagree. In fact, their study suffers from many of the same problems that have plagued other work in this area. Although the authors repeatedly refer to their study as a prospective cohort study, reporting of caffeine consumption from LMP to interview was retrospective. Further, 59% of the women who miscarried were interviewed after their miscarriage, raising concerns of recall bias. Although the authors state in the Discussion that they performed a stratified analysis looking at the results among women who miscarried before the interview vs after and there were no differences, these data are quite important and should have been reported among the main results of the study. There is some confusion with regard to the selection of “confounders” included in the final models. Although variables such as Jacuzzi use and magnetic field exposure were available in the overall dataset, their relation to caffeine consumption and therefore status as true confounders in this analysis is unclear. We are particularly concerned about the inclusion of history of previous miscarriage as a confounder in the model; something that should have been addressed using more sophisticated techniques such as hierarchical modeling.2 We also question why the authors stratified by a change in caffeine intake during pregnancy and controlled for nausea and vomiting in the final adjusted models. There is a substantial body of literature that suggests that the presence of nausea and vomiting is indicative of a healthy pregnancy3; therefore, controlling for this factor may in effect be controlling for the very outcome being studied, rendering such control uninterpretable.
It is worth noting that Savitz et al4 recently published an article on this same topic. They found little evidence of an association between caffeine consumption before or early in pregnancy and the risk of miscarriage. Their study also involved retrospective reporting, with some of the interviews occurring after the miscarriage. Indeed, in stratifying the results by time of interview, they found evidence of positive associations among those women whose interview occurred after the loss, while there were no associations among those who were interviewed before the loss occurred. f Courtney D. Lynch, PhD, MPH Division of Epidemiology The Ohio State University College of Public Health B218 Starling-Loving Hall 320 W. 10th Ave. Columbus, OH 43210 [email protected] Mark A. Klebanoff, MD, MPH Germaine M. B. Louis, PhD, MS Epidemiology Branch Division of Epidemiology, Statistics and Prevention Research Eunice Kennedy Shriver National Institute of Child Health and Human Development Rockville, MD REFERENCES 1. Weng X, Odouli R, Li DK. Maternal caffeine consumption during pregnancy and the risk of miscarriage: a prospective cohort study. Am J Obstet Gynecol 2008;198:279.e1– e8. 2. Louis GB, Dukic V, Heagerty PJ, Louis TA, Lynch CD, Ryan LM, et al. Analysis of repeated pregnancy outcomes. Stat Methods Med Res 2006;5:103-26. 3. Weigel RM, Weigel MM. Nausea and vomiting of early pregnancy and pregnancy outcome: a meta-analytical review. Br J Obstet Gynaecol 1989;96:1312-8. 4. Savitz DA, Chan RL, Herring AH, Howards PP, Hartmann KE. Caffeine and miscarriage risk. Epidemiology 2008;19:55-62. © 2008 Mosby, Inc. All rights reserved. doi: 10.1016/j.ajog.2008.05.035
Oversight or Trompe l’oeil? TO THE EDITORS: Vercellini et al recently reported that the postoperative use of a low-dose oral contraceptive pill (OCP) reduces the risk of endometrioma recurrence.1 They retrospectively followed up on 277 patients who had undergone laparoscopic excision of ovarian endometriomas and who were offered OCP, and examined the recurrence rate in 3 groups: (1) patients who used OCP for the entire follow-up period (always users); (2) those who used OCP discontinuously (ever users); and (3) those who declined treatment (never users). By showing that group 3 has a significantly higher rate of recurrence than 1 group and 1 that, within group 2, patients used OCP for e16
American Journal of Obstetrics & Gynecology NOVEMBER 2008
ⱖ 12 months have a significantly lower recurrence rate than those who used less than 12 months, they concluded that the OCP used postoperatively is beneficial. Recognizing the possibility of a self-selection bias in patients, they argued that “women taking OCP could have been considered at higher risk of endometrioma recurrence because the suggestion to use postoperative medical treatment would be expected to be more probable after difficult or nonradical surgery than after routine procedures,”1 and hence their results could be conservative. However, a closer look at their presented data suggests that the selection bias is in the direction opposite to what the au-