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Letters to the Editors www.AJOG.org

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O THE EDITORS: We are writing a letter to express ouroncerns with a recent publication in your journal by Cal-eron-Margalit et al, regarding the use of psychotropic medi-ations in pregnancy.1

Our main concern was with the content of the abstract. We areware that although it is not good practice, many individuals readnly the abstracts of journal articles, which are designed to sum-arize the relevant information about the study. There are many

easons for this, including lack of full text access and insufficientime to review the entire article.2 Studying medication use in preg-ancy is complex and sometimes controversial, particularly sur-ounding the use of antidepressants.3

We believe that the authors omitted certain informationrom the abstract that was clear in the text. The authors’ cohortas documented as 2793 women, and they reported that ben-

odiazepine was highly associated with an increased risk of pre-erm delivery. The reporting in the abstract suggested that thentire cohort were psychotropic medication users. It is onlyhen one reads the text, that it becomes apparent that the

ctual sample size of psychotropic medication users was only0.7% (300/2793) of their cohort. In addition, decreasing theample size further, hydroxyzine, an antihistamine, was listeds a psychotropic drug (n � 107). This decreases the sampleize to an even smaller number, which is insufficient to make a

edications during pregnancy: met

95% CI, 1.34 –19.8; P � .017), in the second trimester was 7.39

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12 American Journal of Obstetrics & Gynecology OCTOBER 2010

nly wonder how many health care providers, after readingnly the abstract, may have given their patients inappropriate

nformation. It is important to treat psychiatric illness duringregnancy to ensure the best outcome for both the mother andhild and unambiguous information is necessary in decisionaking regarding appropriate treatment. f

eborah Kennedy, NDdrienne Einarson, RNhe Motherisk Programhe Hospital for Sick Children55 University Ave.oronto, ON M5G 1X8 Canadakennedy@ccnm.edu

EFERENCES. Calderon-Margalit R, Qiu C, Ornoy A, Siscovick DS, Williams MA. Riskf preterm delivery and other adverse perinatal outcomes in relation toaternal use of psychotropic medications during pregnancy. Am J Ob-

tet Gynecol 2009;201:579.e1-8.. Einarson TR, Lee C, Smith R, et al. Quality and content of abstracts inapers reporting about drug exposures during pregnancy. Birth Defectses A Clin Mol Teratol 2006;76:621-8.. Louik C, Lin AE, Werler MM, Hernandez-Diaz S, Mitchell AA. First-rimester use of selective serotonin-reuptake inhibitors and the risk of birthefects. N Engl J Med 2007;356:2675-83.

efinitive conclusion regarding any adverse effects. We can © 2010 Mosby, Inc. All rights reserved. doi: 10.1016/j.ajog.2010.04.043

isk of preterm delivery in relation to maternal use of psychotropic

hodological issues

O THE EDITORS: Despite our appreciation for the work ofalderon-Margalit et al1 carried out recently, we wonderhether the drawn conclusions are legitimate and the estima-

ion of odds ratios (OR) are realistic, in consideration of itsethodological limitations.The authors aimed to explore benzodiazepine and selective

erotonin reuptake inhibitor effect on pregnancy outcomes.rimary outcome of the prospective cohort study was the oddsf preterm delivery among women exposed to psychotropicedications during pregnancy, in comparison to women whoere not exposed.The authors reasonably carried out a multivariate analysis

djusting results for potential confounders and/or effect mod-fiers such as maternal age, race, years of maternal education,

arital status, smoking during pregnancy, preeclampsia, andingleton/multiple pregnancy.

Their results showed that maternal use of benzodiazepine inregnancy was associated with an adjusted OR for pretermelivery as large as 6.79 (95% confidence interval [CI], 4.01–1.5; P � .001). The odds of preterm delivery among exposeds unexposed varied by gestational age at first drug adminis-ration. Adjusted OR before or during first trimester was 5.15

95% CI, 2.35–23.2; P � .001), and in the third trimester was0.1 (95% CI, 4.84 –21.1; P � .001). The overall maternal use ofelective serotonin reuptake inhibitor was associated with amall increase in the risk of preterm delivery, but this result wasot significant (adjusted OR, 1.34; 95% CI, 0.76 –2.36).Our concerns about these results mainly regard possible

onfounding factors or effect modifiers neglected in the mul-ivariate analysis. In fact, preterm delivery is thought to be as-ociated with infection and inflammation.2 Despite previouslinical trials failing to demonstrate the effectiveness of antibi-tic therapy at reducing preterm delivery incidence, strong ev-

dence suggested that infections could contribute to 25% ofreterm birth.2 Based on the latest findings, it seems unreliableo estimate a risk of preterm delivery in a reference population,ithout collecting information on genital tract infections andaginal flora variation. Furthermore, genetic factors have beenemonstrated to predispose to preterm delivery. Women withprevious preterm delivery are 5.6 times more exposed to re-

urrence of preterm than women without a history.3

Although neither infections nor genetic factors could beonsidered causal factors for preterm delivery, we truly believehose factors should be always evaluated when preterm deliv-

ry is considered as primary outcome. f