Beta-Blockers increase the risk of being born small for gestational age or of being institutionalised during infancy R-h Xie, a,b,c Y Guo, b,c D Krewski, d,e,f D Mattison, d,e MC Walker, b,c,f K Nerenberg, g SW Wen b,c,f,h a Department of Obstetrics and Gynaecology, Nanfang Hospital, Southern Medical University, Guangzhou, China b OMNI Research Group, Department of Obstetrics and Gynaecology, University of Ottawa Faculty of Medicine, Ottawa, ON, Canada c Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada d McLaughlin Centre for Population Health Risk Assessment, Institute of Population Health, University of Ottawa, Ottawa, ON, Canada e Risk Sciences International, Ottawa, ON, Canada f Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, ON, Canada g Department of Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada h School of Public Health, Central South University, Changsha, China Correspondence: Dr SW Wen, OMNI Research Group, Department of Obstetrics and Gynecology, University of Ottawa, 501 Smyth Road, Box 241, Ottawa, ON K1H 8L6, Canada. Email swwen@ohri.ca Accepted 19 December 2013. Published Online 17 March 2014. Objective To compare infant outcomes between mothers with hypertension treated by beta-blockers alone and by methyldopa alone during pregnancy. Design Historical cohort study. Setting Saskatchewan, Canada. Population Women who delivered a singleton birth in Saskatchewan during the periods from 1 January 1980 to 30 June 1987 or from 1 January 1990 to 31 December 2005 (women who delivered between 1 July 1987 and 31 December 1989 were excluded because the information recorded on maternal drug use during pregnancy is incomplete) with a diagnosis of a hypertensive disorder during pregnancy, and who were dispensed only beta-blockers (n = 416) or only methyldopa (n = 1000). Methods Occurrences of adverse infant outcomes were compared between women who received beta-blockers only and women who received methyldopa only during pregnancy, first in all eligible women, and then in women with chronic hypertension and in women with gestational hypertension or pre-eclampsia/eclampsia, separately. Multiple logistic regression analyses were performed to adjust for potential confounding. Main outcome measures Small for gestational age (SGA) < 10th percentile, SGA < 3rd percentile, preterm birth, stillbirth, institutionalisation for respiratory distress syndrome (RDS), sepsis, seizure during infancy, and infant death. Results Adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) for infants born to mothers with chronic hypertension who were dispensed beta-blockers only, as compared with infants born to mothers who were dispensed methyldopa only, during pregnancy were: 1.95 (1.21–3.15), 2.17 (1.06–4.44), and 2.17 (1.09–4.34), respectively, for SGA < 10th percentile, SGA < 3rd percentile, and being institutionalised during infancy. Conclusions For infants born to mothers with chronic hypertension, compared with those treated by methyldopa alone, those treated by beta-blockers appear to be at increased rates of SGA and hospitalisation during infancy. Keywords Adrenergic beta-antagonists, hypertension, infant, institutionalised, small for gestational age. Please cite this paper as: Xie R-h, Guo Y, Krewski D, Mattison D, Walker MC, Nerenberg K, Wen SW. Beta-Blockers increase the risk of being born small for gestational age or of being institutionalised during infancy. BJOG 2014;121:1090–1096. Introduction Beta-blocking and alpha-blocking drugs are commonly used to treat hypertension during pregnancy. 1–4 Frequently used beta-blockers include acebutolol, atenolol, labetalol, mepindolol, metoprolol, pindolol, oxprenolol, and pro- pranolol; clonidine and (mostly) methyldopa are used as alpha agonists. 1–4 Previous studies have suggested that pregnancy exposure to beta-blockers may be associated with low birthweight. 5,6 In a systematic review of 13 clinical trials, Magee and Duley compared birth outcomes between pregnancies exposed to oral beta-blockers with those exposed to methyldopa, and found that the overall risk of small for gestational age (SGA) in pregnancies using 1090 ª 2014 Royal College of Obstetricians and Gynaecologists DOI: 10.1111/1471-0528.12678 www.bjog.org Epidemiology