http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, Early Online: 1 ! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2014.930428
LETTER TO THE EDITOR
Low-dose aspirin for the prevention of adverse pregnancy outcomes in women with elevated alpha-fetoprotein J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Chulalongkorn University on 12/25/14 For personal use only.
Suzanne Demers1, Ste´phanie Roberge2, and Emmanuel Bujold1,2 1
Department of Obstetrics & Gynecology and 2Department of Social and Preventive Medicine, Faculty of Medicine, Universite´ Laval, Que´bec, QC, Canada
We congratulate Khazardoost et al. [1] for their randomized trial showing reductions of early-onset delivery and other adverse pregnancy outcomes by aspirin in women with elevated mid-trimester alpha-fetoprotein (AFP). Their findings are in agreement with our previous meta-analyses [2–5]. While we observed significantly-decreased adverse perinatal outcomes when low-dose aspirin was initiated before 16 weeks’ gestation, this is a rare study that specifically evaluated the benefits of aspirin between 16 and 20 weeks’ gestation [2]. We would like to clarify some important points and emphasize the importance of gestational age at treatment initiation. Although it seems clear in the Methods section that eligible women were randomized to receive either 80 mg of aspirin or not, the authors concluded in the Discussion that 100 mg of aspirin taken daily between 15 and 18 weeks’ generation prevented adverse pregnancy outcomes. Could they clarify the dosage that was administered, whether or not placebo was provided to keep the obstetricians blinded to treatment allocation and, if not, whether women in the control group were asked about personal consumption of low-dose aspirin after randomization? Finally, since the mechanisms of preterm birth prevention with low-dose aspirin remain unclear, except for cases of preterm preeclampsia, could the authors provide the reasons for delivery before 34 weeks in both groups: were they spontaneous or indicated (preeclampsia, fetal growth restriction, etc.) preterm deliveries [4,6]?
Since low-dose aspirin started before 16 weeks has been associated with reduction of placenta-mediated pregnancy outcomes, we strongly encourage clinical laboratories and healthcare providers – using mid-trimester AFP for Down’s syndrome screening – to recommend blood sampling as early as possible (14–15 weeks’ gestation) and to find timely ways to contact women with elevated AFP levels.
References 1. Khazardoost S, Mousavi S, Borna S, et al. Effect of aspirin in prevention of adverse pregnancy outcome in women with elevated alpha-fetoprotein. J Matern Fetal Neonatal Med 2014;27:561–5. 2. Bujold E, Morency AM, Roberge S, et al. Acetylsalicylic acid for the prevention of preeclampsia and intra-uterine growth restriction in women with abnormal uterine artery Doppler: a systematic review and meta-analysis. J Obstet Gynaecol Can 2009; 31:818–26. 3. Bujold E, Roberge S, Lacasse Y, et al. Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy: a meta-analysis. Obstet Gynecol 2010;116:402–14. 4. Roberge S, Villa P, Nicolaides K, et al. Early administration of lowdose aspirin for the prevention of preterm and term preeclampsia: a systematic review and meta-analysis. Fetal Diagn Ther 2012;31: 141–6. 5. Roberge S, Nicolaides KH, Demers S, et al. Prevention of perinatal death and adverse perinatal outcome using low-dose aspirin: a meta-analysis. Ultrasound Obstet Gynecol 2013;41:491–9. 6. Bujold E, Roberge S, Tapp S, Giguere Y. Opinion & hypothesis could early aspirin prophylaxis prevent against preterm birth? J Matern Fetal Neonatal Med 2011;24:966–7.
Address for correspondence: Emmanuel Bujold, MD, MSc, FRCSC, Professor, Department of Obstetrics and Gynecology, Faculty of Medicine, Universite´ Laval, 2705 boulevard Laurier, Que´bec, QC, G1V 4G2, Canada. E-mail: [email protected]
LETTER TO THE EDITOR
Low-dose aspirin for the prevention of adverse pregnancy outcomes in women with elevated alpha-fetoprotein J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Chulalongkorn University on 12/25/14 For personal use only.
Suzanne Demers1, Ste´phanie Roberge2, and Emmanuel Bujold1,2 1
Department of Obstetrics & Gynecology and 2Department of Social and Preventive Medicine, Faculty of Medicine, Universite´ Laval, Que´bec, QC, Canada
We congratulate Khazardoost et al. [1] for their randomized trial showing reductions of early-onset delivery and other adverse pregnancy outcomes by aspirin in women with elevated mid-trimester alpha-fetoprotein (AFP). Their findings are in agreement with our previous meta-analyses [2–5]. While we observed significantly-decreased adverse perinatal outcomes when low-dose aspirin was initiated before 16 weeks’ gestation, this is a rare study that specifically evaluated the benefits of aspirin between 16 and 20 weeks’ gestation [2]. We would like to clarify some important points and emphasize the importance of gestational age at treatment initiation. Although it seems clear in the Methods section that eligible women were randomized to receive either 80 mg of aspirin or not, the authors concluded in the Discussion that 100 mg of aspirin taken daily between 15 and 18 weeks’ generation prevented adverse pregnancy outcomes. Could they clarify the dosage that was administered, whether or not placebo was provided to keep the obstetricians blinded to treatment allocation and, if not, whether women in the control group were asked about personal consumption of low-dose aspirin after randomization? Finally, since the mechanisms of preterm birth prevention with low-dose aspirin remain unclear, except for cases of preterm preeclampsia, could the authors provide the reasons for delivery before 34 weeks in both groups: were they spontaneous or indicated (preeclampsia, fetal growth restriction, etc.) preterm deliveries [4,6]?
Since low-dose aspirin started before 16 weeks has been associated with reduction of placenta-mediated pregnancy outcomes, we strongly encourage clinical laboratories and healthcare providers – using mid-trimester AFP for Down’s syndrome screening – to recommend blood sampling as early as possible (14–15 weeks’ gestation) and to find timely ways to contact women with elevated AFP levels.
References 1. Khazardoost S, Mousavi S, Borna S, et al. Effect of aspirin in prevention of adverse pregnancy outcome in women with elevated alpha-fetoprotein. J Matern Fetal Neonatal Med 2014;27:561–5. 2. Bujold E, Morency AM, Roberge S, et al. Acetylsalicylic acid for the prevention of preeclampsia and intra-uterine growth restriction in women with abnormal uterine artery Doppler: a systematic review and meta-analysis. J Obstet Gynaecol Can 2009; 31:818–26. 3. Bujold E, Roberge S, Lacasse Y, et al. Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy: a meta-analysis. Obstet Gynecol 2010;116:402–14. 4. Roberge S, Villa P, Nicolaides K, et al. Early administration of lowdose aspirin for the prevention of preterm and term preeclampsia: a systematic review and meta-analysis. Fetal Diagn Ther 2012;31: 141–6. 5. Roberge S, Nicolaides KH, Demers S, et al. Prevention of perinatal death and adverse perinatal outcome using low-dose aspirin: a meta-analysis. Ultrasound Obstet Gynecol 2013;41:491–9. 6. Bujold E, Roberge S, Tapp S, Giguere Y. Opinion & hypothesis could early aspirin prophylaxis prevent against preterm birth? J Matern Fetal Neonatal Med 2011;24:966–7.
Address for correspondence: Emmanuel Bujold, MD, MSc, FRCSC, Professor, Department of Obstetrics and Gynecology, Faculty of Medicine, Universite´ Laval, 2705 boulevard Laurier, Que´bec, QC, G1V 4G2, Canada. E-mail: [email protected]
