Table 1.

Characteristics of 12 studies that examine the association between beta-blocker exposure and congenital malformations^* (CC=case-control, RC=retrospective cohort, PC= prospective cohort).

Author, Year	Study design	Country/Data source	Specific beta-blocker	Period of pregnancy of drug use	Indication of drug use	Class of anomalies	Patients with DM excluded/adj usted†	Potential recall bias
Banhidy 201111	CC	Hungary: Hungarian Congenital Abnormality Registry (HCAR), maternal information: prospective medical records, retrospective self-report	Metoprolol, oxprenolol, pindolol, propranolol	Included 1st trimester	Chronic HTN/other indications	All within 3 months of live birth excluding genetic or chromosomal aberrations	Not clear	Yes
Caton 200912	CC	USA: Population-based birth defects surveillance systems; maternal information: interview	Any	1 month preconception through the third month of pregnancy	HTN	CV excluding patent ductus arteriosus (PDA), patent foramen ovale, or recognized single gene or chromosome abnormalities	Yes	Yes
Caton 200813	CC	USA: Population- based birth defects surveillance systems; maternal information: interview	Any	1 month preconception through month 4 post- conception	HTN	Severe hypospadias excluding chromosome/gene abnormality or intersex condition	Yes	Yes
Cedergren 2002 14	CC	Sweden: Swedish Register Study, Child Cardiology Register, Medical Birth Register, medical records	Any	10 - 12 weeks	Not specified	Cardiac defects referred within one year of birth, excluding PDA and single umbilical artery	No	No
Medveczky 2004a 9	CC	Hungary: HCAR; exposure data: retrospective mailed questionnaire, prenatal log/nurse visits	Oxprenolol	Second month	Not specified	Non-syndromic NT defects within 3 months of birth or pregnancy termination	Yes	Yes
Medveczky 2004b 9	CC	Hungary: HCAR; exposure data: retrospective mailed questionnaire, prenatal log/nurse visits	Pindolol	Second month	Not specified	Non-syndromic NT defects within 3 months of birth or pregnancy termination	Yes	Yes
Nakhai- Pour 201015-17	CC	Canada: Quebec Pregnancy Registry	Selective and non- selective	First trimester	HTN	Major congenital malformations within first year of life	Yes	No
Puho 2006a8	CC	Hungary: HCAR, maternal information: prospective medical records and retrospective self-report	Metoprolol	Third to fourth months§	HTN	Posterior cleft palate within 3 months of birth or pregnancy termination	Yes	Yes
Puho 2006b8	CC	Hungary: HCAR, maternal information: prospective medical records and retrospective self-report	Oxprenolol	Third to fourth months§	HTN	Posterior cleft palate within 3 months of birth or pregnancy termination	Yes	Yes
Puho 2006c8	CC	Hungary: HCAR, maternal information: prospective medical records and retrospective self-report	Oxprenolol	Second to third months	HTN	Cleft lip and palate 3 months of birth or pregnancy termination	Yes	Yes
Quiesser- Luft 1996 18	CC	Germany: Mainz birth defect monitoring system, maternal & infant medical records	Any	First three months	Not specified	At least one major malformation within first week of life, excluding spontaneous abortions	No	No
Davis 201120	RC	USA: HMO Research Network records	Any	First trimester	HTN	All congenital anomalies within first year of life	No	No
Eric 2009 22	PC	Serbia: Maternal questionnaire, neonatal or fetal physical or pathologic examination	Propranolol and metoprolol	First trimester	CV disorders	Minor or major anomalies at birth	No	Yes
Kallen 200321‡	RC	Sweden: Swedish Medical Registry	Any	first trimester	Not specified	CV (except PDA and single umbilical artery)	No	No
Lennestal 200923	RC	Sweden: Swedish Medical Birth Register, Congenital Malformation Register, Hospital Discharge Register	Any	Early pregnancy	HTN	CV	Yes	No

^*Sipek et al.¹⁹ is excluded from the table.

^†Whether diabetes was excluded/adjusted in any analyses in the paper. For specific information on beta-blocker use, see Supplemental Table S1.

^‡This study not included in the meta-analysis; more recent study by Lennestal et al. with extended follow-up using the same data set is included.

^§3^rd to 4^th months of pregnancy included due to timing of fetal palate formation.