A Swedish Population-based Study of Adverse Birth Outcomes among Pregnant Women Treated with Buprenorphine or Methadone: Preliminary Findings.
BACKGROUND
Untreated opioid dependence in pregnant women is associated with adverse birth outcomes. Buprenorphine and methadone are options for opioid agonist medication-assisted treatment during pregnancy.


OBJECTIVE
The aim of this study was to describe adverse birth outcomes observed with buprenorphine or methadone treatment compared to the general population in Sweden.


METHODS
Pregnant women and their corresponding births during 2005-2011 were identified in the Swedish Medical Birth Register. Data on stillbirth, neonatal/infant death, mode of delivery, gestational age at birth, Apgar score, growth outcomes, neonatal abstinence syndrome, and congenital malformations were examined. Frequencies were compared using two-sided Fisher's exact tests. Unadjusted estimates of birth outcomes for women treated with buprenorphine or methadone were compared to the registered general population.


RESULTS
A total of 746,257 pregnancies among 538,178 unique women resulted in 746,485 live births. Among the 194 women treated with buprenorphine (N = 176) or methadone (N = 52), no stillbirths or neonatal/infant deaths occurred. Neonatal abstinence syndrome developed in 23.3% and 38.5% of infants born to mothers treated with buprenorphine and methadone, respectively. The frequency of the selected adverse birth outcomes assessed in women treated with buprenorphine as compared to the general population was not significantly different. However, a significantly higher frequency of preterm birth and congenital malformations was observed in women treated with methadone as compared to the general population. Compared with the general population, methadone-treated women were significantly older than buprenorphine-treated women, and both treatment groups began prenatal care later, were more likely to smoke cigarettes, and did not cohabitate with the baby's father.


CONCLUSIONS
An increased frequency of the selected adverse birth outcomes was not observed with buprenorphine treatment during pregnancy. Twofold increased frequency of preterm birth [2.21 (1.11, 4,41)] and congenital malformations [2.05 (1.08, 3.87)] was observed in the methadone group, which may be partly explained by older average maternal age and differences in other measured and unmeasured confounders.
Consultant, Venebio Group, LLC, Richmond, VA, USA.
Keele E
KE
Wurst
Consultant, Venebio Group, LLC, Richmond, VA, USA.
Barbara K
BK
Zedler
Consultant, Venebio Group, LLC, Richmond, VA, USA.
Andrew R
AR
Joyce
Consultant, Venebio Group, LLC, Richmond, VA, USA.
Maciek
M
Sasinowski
Consultant, Venebio Group, LLC, Richmond, VA, USA.
E Lenn
EL
Murrelle
buprenorphine; methadone; opioid agonist medication-assisted treatment; opioid dependence; opioid use disorder; pregnancy
Acta Paediatr. 1996 Jul;85(7):843-8
8819552
Drug Alcohol Depend. 2008 Jul 1;96(1-2):69-78
18355989
J Subst Abuse Treat. 2003 Jun;24(4):363-7
12867211
Drug Alcohol Depend. 2005 Jul;79(1):1-10
15943939
Am J Obstet Gynecol. 2004 Dec;191(6):1885-97
15592269
N Engl J Med. 2010 Dec 9;363(24):2320-31
21142534
BJOG. 2014 Nov;121(12):1471-81
24612301
J Addict Med. 2015 Mar-Apr;9(2):81-6
25622120
Yonsei Med J. 2008 Oct 31;49(5):705-13
18972589
Clin Pharmacokinet. 2004;43(5):329-40
15080765
Drug Alcohol Depend. 2013 Jan 1;127(1-3):200-6
22841456
Arch Pediatr. 1999 Nov;6(11):1179-85
10587741
Eur J Clin Pharmacol. 2011 Oct;67(10):1053-9
21538146
Obstet Gynecol. 2012 May;119(5):1070-6
22525931
Drug Alcohol Depend. 2013 Aug 1;131(3):271-7
23279924
Drug Alcohol Depend. 2006 May 20;82(3):250-7
16257138
Obstet Gynecol. 2014 Jan;123(1):104-12
24463670
Euro Surveill. 2009 Mar 05;14(9):33-6
19317968
Subst Abuse. 2015 Oct 09;9(Suppl 2):5-11
26512202
J Addict Med. 2012 Dec;6(4):258-64
23135165
Acta Obstet Gynecol Scand. 2003 Jun;82(6):491-2
12780418
Eur Addict Res. 2009;15(3):128-34
19332991
J Addict Dis. 2010 Apr;29(2):175-91
20407975
Ultrasound Obstet Gynecol. 2013 Dec;42(6):634-43
23630102
BMJ. 2008 Jun 7;336(7656):1303-5
18535073
Hum Psychopharmacol. 2011 Aug;26(6):412-21
21823171
Obstet Gynecol. 1998 Nov;92(5):854-8
9794682
Cochrane Database Syst Rev. 2013 Dec 23;(12):CD006318
24366859
Addiction. 2004 Feb;99(2):209-14
14756713
Addiction. 2012 Aug;107(8):1482-92
22340442
Arch Dis Child Fetal Neonatal Ed. 2015 Nov;100(6):F486-91
25972442
Addiction. 2006 Feb;101(2):275-81
16445556
J Clin Psychopharmacol. 2008 Jun;28(3):279-88
18480684
Psychiatr Clin North Am. 2012 Jun;35(2):441-60
22640765
Obstet Gynecol. 2015 Feb;125(2):363-8
25569005
CMAJ. 2005 Sep 13;173(6):615-8
16157725
Am J Med Genet A. 2011 Sep;155A(9):2137-45
21815253
Pediatr Cardiol. 2003 May-Jun;24(3):195-221
12632215