Obstetrics and Gynecology International Drugs during Pregnancy and Lactation: New Solutions to Serious Challenges Guest Editors: Gideon Koren, Shannon Clark, and Doreen Matsui Drugs during Pregnancy and Lactation: New Solutions to Serious Challenges Obstetrics and Gynecology International Drugs during Pregnancy and Lactation: New Solutions to Serious Challenges Guest Editors: Gideon Koren, Shannon Clark, and Doreen Matsui Copyright © 2012 Hindawi Publishing Corporation. All rights reserved. This is a special issue published in “Obstetrics and Gynecology International.” All articles are open access articles distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Editorial Board Sean Blackwell, USA Howard D. Homesley, USA Julian T. Parer, USA Diane C. Bodurka, USA Shi-Wen Jiang, USA Faustino R. Perez-L´ opez,´ Spain Curt W. Burger, The Netherlands Marc J. N. C. Keirse, Australia Tonse N.K. Raju, USA Linda D. Cardozo, UK Russell K. Laros Jr., USA Neal S. Rote, USA Nancy Chescheir, USA Jonathan Ledermann, UK Giovanni Scambia, Italy Robert Coleman, USA Kimberly K. Leslie, USA Peter E. Schwartz, USA W. T. Creasman, USA Lawrence D. Longo, USA John J. Sciarra, USA Mary E. D’Alton, USA G. A. Macones, USA J. L. Simpson, USA Gian Carlo Di Renzo, Italy Everett Magann, USA Anil Sood, USA Keith A. Eddleman, USA James A. McGregor, USA Wiebren A. A. Tjalma, Belgium Edmund F. Funai, USA Liselotte Mettler, Germany J. R. Van Nagell, USA Thomas Murphy Goodwin, USA Daniel R. Mishell, USA John G. van Vugt, The Netherlands WilliamA.Grobman,USA Bradley J. Monk, USA M. A. Williams, USA Enrique Hernandez, USA John J. Moore, USA Deborah A. Wing, USA Thomas Herzog, USA J. C. Morrison, USA Judith K. Wolf, USA Wolfgang Holzgreve, Switzerland Errol R. Norwitz, USA Edward V. Younglai, Canada Contents Drugs during Pregnancy and Lactation: New Solutions to Serious Challenges,GideonKoren, Shannon Clark, and Doreen Matsui Volume 2012, Article ID 206179, 2 pages Circulating Unmetabolized Folic Acid: Relationship to Folate Status and Effect of Supplementation, Carolyn Tam, Deborah O’Connor, and Gideon Koren Volume 2012, Article ID 485179, 17 pages Opioid Dependent and Pregnant: What Are the Best Options for Mothers and Neonates?, Annemarie Unger, Verena Metz, and Gabriele Fischer Volume 2012, Article ID 195954, 6 pages Effect of Domperidone on Insufficient Lactation in Puerperal Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials,AllaOsadchy,MylaE.Moretti,andGideonKoren Volume 2012, Article ID 642893, 7 pages The Effects of Maternal Supplementation of Polyunsaturated Fatty Acids on Visual, Neurobehavioural, and Developmental Outcomes of the Child: A Systematic Review of the Randomized Trials, Andrea Lo, Julianna Sienna, Eva Mamak, Nada Djokanovic, Carol Westall, and Gideon Koren Volume 2012, Article ID 591531, 9 pages Adherence with Drug Therapy in Pregnancy,DoreenMatsui Volume 2012, Article ID 796590, 5 pages Breastfeeding Self-Efficacy and the Use of Prescription Medication: A Pilot Study, Cynthia Mannion and Deborah Mansell Volume 2012, Article ID 562704, 8 pages The Fetal Safety of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers, Myla E. Moretti, Daniela Caprara, Irina Drehuta, Emily Yeung, Stefanie Cheung, Lisa Federico, and Gideon Koren Volume 2012, Article ID 658310, 6 pages Selective Serotonin Reuptake Inhibitors in Human Pregnancy: To Treat or Not to Treat?, Orna Diav-Citrin and Asher Ornoy Volume 2012, Article ID 698947, 12 pages Ethical Issues in Pharmacologic Research in Women Undergoing Pregnancy Termination: A Systemic Review and Survey of Researchers, Christelle Gedeon, Alejandro A. Nava-Ocampo, and Gideon Koren Volume 2012, Article ID 724591, 5 pages Review of NVP and HG and Early Pharmacotherapeutic Intervention, Shannon M. Clark, Maged M. Costantine, and Gary D. V. Hankins Volume 2012, Article ID 252676, 8 pages The Problem of Confounding in Studies of the Effect of Maternal Drug Use on Pregnancy Outcome, Bengt Kall¨ en´ Volume 2012, Article ID 148616, 16 pages Hindawi Publishing Corporation Obstetrics and Gynecology International Volume 2012, Article ID 206179, 2 pages doi:10.1155/2012/206179 Editorial Drugs during Pregnancy and Lactation: New Solutions to Serious Challenges Gideon Koren,1, 2 Shannon Clark,3 and Doreen Matsui1 1 Department of Pediatrics, University of Western Ontario, London, ON, Canada N6A 5W9 2 Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada M5G 1X8 3 University of Texas, Galveston, TX 77555, USA Correspondence should be addressed to Gideon Koren, gidiup [email protected] Received 2 November 2011; Accepted 2 November 2011 Copyright © 2012 Gideon Koren et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Ethically, it is very difficult to use the classical paradigms of even if they exist, occur at very low rates and are outweighed drug studies in pregnancy, due to the potential fetal risks of by the maternal benefits of these drugs. prospective exposure of the mother and fetus to chemicals M. Moretti and colleagues focus on another controversial for which safety has not been confirmed. This special issue area—the fetal safety of ACE inhibitors, commonly used presents new approaches and offers novel solutions to serious for hypertension. By including a control group matched for challenges, from the use of antidepressants in pregnancy to the hypertensive morbidity, they strengthen the growing domperidone in enhancing lactation, from the potential fetal body of evidence suggesting no increased fetal risks after advantages of polyunsaturated fatty acids to the potential risk first trimester exposure to ACE inhibitors. With convincing of drugs of abuse. evidence that neonatal folic acid supplementation and forti- The majority of pregnant women use medications during fication can prevent neural tube defects, a fear has emerged pregnancy either before recognizing they have conceived or that too much circulating folate may increase the risk of due to the need to treat medical conditions that may affect cancer as an adverse effect of unmetabolized folic acid. C. maternal and fetal well-being. Due to the potential fetal risks Tam and colleagues document that levels of unmetabolized of drugs, very few randomized controlled trials are being folic acid do not increase in women even when taking conducted in early pregnancy, and the numbers are scarce 5 mg daily. This detailed biochemical study adds important even after embryogenesis has been completed. As a result, reassurance that short period use of even 5 mg folate (which women are typically orphaned from the benefits of new ther- is needed in groups of women at high risk for neural tube apeutic modalities. Yet, with women tending to postpone defects) is safe to the expecting mother. the age of starting a family, substantially larger numbers of S. M. Clark and colleagues update the reader on the women experience chronic conditions that necessitate drug advances in treating the most common condition in preg- therapy. nancy—morning sickness. Even today, a large proportion of This issue focuses on major challenges in the area of pregnant women are afraid to treat the symptoms of nausea drug therapy during pregnancy and lactation, looking for and vomiting of pregnancy due to unjustified perception evidence of safety and effectiveness with the use of a variety of of fetal risks. S. M. Clark et al. match the evidence of ef- research methodologies that try to replace the gold standard fectiveness with that of fetal safety, documenting that in 2012 of randomized clinical trials. there is no logical reason for a woman not to be managed O. Diav-Citrin and A. Ornoy tackle what is probably the safely for this condition. biggest contemporary controversy—the fetal safety of anti- Breastfeeding is the ideal method of infant nutrition; depressants. Through painstaking review of over 30 studies, however, not rarely women cannot establish effective milk they come to the conclusion that fetal and neonatal risks, flow to ensure optimal feeding. Two research papers in 2 Obstetrics and Gynecology International this special issue address this problem, relating directly to We hope that you, the reader, will find this special issue the dopaminergic agent domperidone. A. Osadschy and stimulating and, as important, relevant to your practice. colleagues use a meta-analytic technique to provide evidence Gideon Koren that the existing, small studies prove the effectiveness of Shannon Clark the drug in improving milk production. C. Mannion et al., Doreen Matsui bringing the important angle of lactation consultants, ex- plore in a pilot study determinants of success and failure in establishing breastfeeding. Three papers in this issue explore in-depth methodolog- ical issues which challenge different aspects of drug therapy in pregnancy. B. Kall¨ en´ brings his many years of experience in pharmacoepidemiology to the critical discussion of con- founders which may affect the interpretation of administra- tive data bases. These prescription databases, when linked with databases of pregnancy outcome, create a potentially powerful tool in exploring fetal safety of drugs. However, this method is challenged by a large number of serious