1 Department of Medicine, University of Helsinki, Helsinki, Finland.
2 Department of Pediatrics, University of Helsinki, Helsinki, Finland.
3 Department of Obstetrics and Gynecology, University of Helsinki, Helsinki, Finland.
We thank Hughes et al. (1) for their interest in our study (2), but we do not think their concerns affect the reliability of our results.
The first study (3) was performed at a secondary-level hospital with less research activity, whereas the later study (2) was done at a university clinic with more competing research plans. Therefore, we had a real concern that a complicated study plan could be met with problems in compliance. We cannot exclude that the possibility that, for example, licorice effects on blood pressure could be one mechanism behind the licorice-gestational age connection, but this was not supported by the findings of the first, larger study.
Methods used for determination of gestational age were reliable and consistent in the study. As a part of the follow-up routine (today and at the time of the study), all pregnant women in Helsinki undergo vaginal ultrasonography at week 1213 for determination of gestational age. Moreover, at week 19, a second morphologic assessment is performed. These data are marked in hospital records, and midwives are aware of them.
The selection of cases and controls was based on preterm status. As we stated in our report (2), only twin births, elective cesarean section, induced delivery, and chorioamnionitis were excluded. With respect to licorice effects, this is probably conservative, because preterm birth is multifactorial and further exclusion of cases clearly not related to licorice consumption might have strengthened the observed association. Handling of age in different ways in the analyses did not affect the main conclusions.
It is true that assessment of licorice consumption was retrospective, but the question was asked during the days postpartum. With regard to mechanisms, licorice consumption at the end of pregnancy is probably the most important. If licorice consumption changes during pregnancy, a prospective study would have been unreliable. The best alternative would have been to ask about consumption during various stages of pregnancy, but this was not possible in the present study. On the other hand, our pilot study in antenatal clinics (briefly described in our first report (3)) suggested that consumption of licorice would be similar during the various stages of pregnancy. We do not think that asking the womens partners about licorice consumption would have given us further information on licorice consumption. Licorice consumption, even during pregnancy, is not something to be ashamed of in Finland, and therefore we cannot see why the women would not have given a truthful account. Possible pitfalls of self-reports are well-known, but they apply to controls and cases alike.
Finally, the very essence of our study was that the measurement of glycyrrhizin intake was based on available and accurate information on the amount of glycyrrhizin in various brands of licorice. The names of the brands consumed and the weekly consumption of each were asked about in the questionnaire.
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