Li et al. Respond to "No Link between Hot Tubs and Miscarriage"

De-Kun Li , Teresa Janevic, Roxana Odouli and Liyan Liu

From the Division of Research, Kaiser Foundation Research Institute, Kaiser Permanente, Oakland, CA.

Received for publication July 29, 2003; accepted for publication July 31, 2003.

Observational epidemiologic studies are subject to limitations that are often difficult to quantify and therefore are subject to interpretation. It was our judgment that despite the limitations of our study (1), the observed association between the use of hot tubs or Jacuzzis (any type of whirlpool bath; Jacuzzi Brands, Inc., West Palm Beach, Florida) during pregnancy and the risk of miscarriage was valid enough to be published. This judgment was based not only on the findings presented in our paper but also on the findings of other associations (prenatal exposure to magnetic fields and use of nonsteroidal anti-inflammatory drugs) derived from the same study cohort (2, 3). The findings of the risk of miscarriage associated with other exposures (magnetic fields and nonsteroidal anti-inflammatory drugs) have been corroborated by other studies (4, 5). Even some of the findings reported in our study (e.g., a lack of association with fever) were confirmed by a recent cohort study (6).

Nonetheless, reasonable minds differ. In this issue of the Journal, Hertz-Picciotto and Howards (7) present their judgment on the impact of potential biases and conclude that those limitations undermine our conclusion (1). Our paper addressed many of those criticisms. The new concern of residual confounding due to maternal age was also not supported by our data: the hazard ratio remained essentially unchanged after a linear term for maternal age of >=25 years was used, as suggested by Hertz-Picciotto and Howards (hazard ratio = 1.9, 95 percent confidence interval: 1.2, 2.9). In addition, we realize that the difference in judgment of the impact of those limitations stems not only from the different assumptions for the potential biases but also from the choice of interpreting the results. For example, it is puzzling that, given the results presented in their table 2 (derived from our paper), they would have concluded that "the prospective portion of the study shows essentially no association at all" (7, p. 939). The hazard ratios were consistent regardless of whether the interviews were conducted before or after miscarriage. The hazard ratio of 3.2, based on 2,331 person-days from the exposed women and 24,214 person-days from the unexposed women, remained borderline significant (95 percent confidence interval: 1.0, 10.3) despite the reduced sample size due to splitting women into prospective and retrospective groups. Furthermore, while Hertz-Picciotto and Howards attributed our findings to recall bias, they failed to explain why the recall bias only existed for miscarriage before 10 weeks of gestation, for there was no association for miscarriage beyond 10 weeks of gestation (refer to their table 2). A higher risk associated with use of a hot tub or Jacuzzi for early miscarriage (<10 weeks of gestation) makes good biologic sense; however, it does not support the argument for recall bias.

Ultimately, the validity of our findings (1) will be determined by the findings of replication studies that overcome some of the limitations. Therefore, we would encourage other investigators, including critics of our findings, to conduct better studies to confirm or refute our findings.


    NOTES
 
Correspondence to Dr. De-Kun Li, Division of Research, Kaiser Foundation Research Institute, Kaiser Permanente, 2000 Broadway, Oakland, CA 94612 (e-mail: dkl{at}dor.kaiser.org). Back


    REFERENCES
 TOP
 REFERENCES
 

  1. Li DK, Janevic T, Odouli R, et al. Hot tub use during pregnancy and the risk of miscarriage. Am J Epidemiol 2003;158:931–7.[Abstract/Free Full Text]
  2. Li DK, Odouli R, Wi S, et al. A population-based prospective cohort study of personal exposure to magnetic fields during pregnancy and the risk of miscarriage. Epidemiology 2002;13:9–20.[CrossRef][ISI][Medline]
  3. Li DK, Liu L, Odouli R. Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk of miscarriage: population based cohort study. BMJ 2003;327:368–72.[Abstract/Free Full Text]
  4. Lee GM, Neutra RR, Hristova L, et al. A nested case-control study of residential and personal magnetic field measures and miscarriages. Epidemiology 2002;13:21–31.[CrossRef][ISI][Medline]
  5. Nielsen GL, Sorensen HT, Larsen H, et al. Risk of adverse birth outcome and miscarriage in pregnant users of non-steroidal anti-inflammatory drugs: population based observational study and case-control study. BMJ 2001;322:266–70.[Abstract/Free Full Text]
  6. Andersen AM, Vastrup P, Wohlfahrt J, et al. Fever in pregnancy and risk of fetal death: a cohort study. Lancet 2002;360:1552–6.[CrossRef][ISI][Medline]
  7. Hertz-Picciotto I, Howards PP. Invited commentary: hot tubs and miscarriage—methodological and substantive reasons why the case is weak. Am J Epidemiol 2003;158:938–40.[Free Full Text]

Related articles in Am. J. Epidemiol.:

Hot Tub Use during Pregnancy and the Risk of Miscarriage
De-Kun Li, Teresa Janevic, Roxana Odouli, and Liyan Liu
Am. J. Epidemiol. 2003 158: 931-937. [Abstract] [FREE Full Text]  

Invited Commentary: Hot Tubs and Miscarriage—Methodological and Substantive Reasons Why the Case Is Weak
Irva Hertz-Picciotto and Penelope P. Howards
Am. J. Epidemiol. 2003 158: 938-940. [Extract] [FREE Full Text]  




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