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Table 1 Case-control studies reporting on the association of ARM and the maternal use of medical drugs

From: Maternal drug use and the risk of anorectal malformations: systematic review and meta-analysis

  Study population  
No. participants
Ref. First author, year Country Cases Controls Age range Setting, control type Data acquisition (period) Assessed medical drug(s)
[28] Zwink, 2016 Germany 158 474a < 18 - ≥30 population-based,
no major birth defects
Data from the German Network for congenital uro-rectal malformations and Malformation Monitoring Centre Saxony-Anhalt of the Otto-von-Guericke University in Magdeburg (2009–2011) Folic acid, multivitamins
[52] Furu, 2015 Norway 799 2,303,647 ≤24 - ≥45 population-based, all births Data from nationwide Nordic health registers (Denmark, Finland, Iceland, Norway, Sweden) (1996–2010) Antidepressants (any SSRI, citalopram,
sertraline)
[73] Garne, 2015 Denmark 772
265c
53,402 < 25 - ≥40 population-based,
non-chromosomal and
chromosol anomalies
Data from the EUROmediCAT registries
(1995–2010)
Anti-asthma medication (any asthma
medication, inhaled ß2-agonists, inhaled corticosteroids)
[50] Wemakor, 2015 UK 392 2,177,977 N.A. registry-based,
other congenital
malformations
Data from 12 EUROCAT congenital anomalies registries (1995–2009) Antidepressants (any SSRI, fluoxetine,
paroxetine, citalopram, sertraline,
escitalopram)
[53] Zwink and Choinitzki, 2015 Germany 123 140 < 18 - ≥30 population-based,
other congenital
malformationsa
Data from the German Network for congenital uro-rectal malformations (2009–2012) and Consortium of Genetic Risk for Esophageal Atresia (2011–2012) Anti-asthma medication, thyroid hormone
supplementations, iron intake, folic acid,
multivitamins
[57] Gilboa, 2014 USA 176 4525 < 20 - ≥35 population-based,
all births
Data from the National Birth Defects Prevention
Study (1997–2005)
Vitamin E
[75] Källén and Wikner, 2014 Sweden 588 48,012 < 20 - ≥45 population-based,
all births
Data from the nationwide Swedish Medical Birth Register (1996–2011) Thyroxin
[41] Wijers, 2014 The Netherlands 643b 714 < 18 - ≥30 hospital-based,
no major birth defects
Questionnaire (1990–2012) Folic acid
[76] Källén, 2013 Sweden 590 69,749 < 20 - ≥45 population-based,
all births
Data from the nationwide Swedish Medical
Birth Register (1996–2011)
Opioids, anticonvulsants, neuroleptics
other than dixyrazine or prochloperazine,
dixyrazine or prochlorperazine,
sedatives or hypnotics, antidepressants
[49] Pasternak, 2013 Denmark 52 1,222,503 N.A. register-based,
all births
Data from the nationwide administrative and
health care registries in Denmark (1997–2011)
Metoclopramide
[54] Polen, 2013 USA 741 8002 < 30 - ≥30 population-based,
no birth defects
Data from the National Birth Defects Prevention
Study (1997–2007)
Antidepressants, venlafaxine
[67] Yau, 2013 USA 274 7606 < 25 - ≥34 population-based,
no birth defects
Data from the Slone Epidemiology Center
Birth Defects Study (1993–2010)
Decongestants (pseudoephedrine)
[59] Lin, 2012 USA 285 6726 < 20 - ≥35 population-based,
no birth defects
Data from the National Birth Defects Prevention
Study (1997–2003)
Anti-asthma medication (bronchodilator use), anti-inflammatory use
[58] Hernandez, 2012 USA 540 5546 < 20 - ≥35 population-based,
no birth defects
Data from the National Birth Defects Prevention
Study (1997–2004)
Non-steroidal anti-inflammatory drugs
(aspirin, ibuprofen, naproxen)
[60] van Gelder, 2011 The Netherlands 16 65,287 < 20 - ≥40 population-based,
no major birth defects
Data from the Norwegian Mother and Child
Cohort Study (1999–2006)
Non-steroidal anti-inflammatory drugs
[55] Reefhuis, 2011 USA 582 6406 < 25 - ≥40 population-based,
no birth defects
Data from the National Birth Defects Prevention
Study (1997–2005)
Clomiphene citrate
[56] Reis and Källén, 2010 Sweden 428 1,062,190 < 20 - ≥45 population-based,
all births
Data from the nationwide Swedish Medical
Birth Register (1995–2007)
Antidepressants
[27] van Rooij, 2010 The Netherlands 85 650 ≥35 hospital-based,
no major birth defects
Questionnaire (cases 1996–2008, controls 1996–2004) Folic acid, multivitamins
[61] Browne, 2009 USA 534 5875 12 - ≥35 population-based,
no birth defects
Data from the National Birth Defects Prevention
Study (1997–2004)
Anti-thyroid medication
[63] Crider, 2009 USA 470 5008 < 18–49 population-based,
no birth defects
Data from the National Birth Defects Prevention
Study (1997–2003)
Antibacterial medication (any antibacterial,
penicillins, erythromycins, nitrofurantoins,
sulfonamides, cephalosporins)
[62] Carter, 2008 USA 209 4774 N.A. population-based,
no birth defects
Data from the National Birth Defects Prevention
Study (1997–2003)
Antifungal drugs
[68] Alwan, 2007 USA 418 4092 < 35 - ≥35 population-based,
no birth defects
Data from the National Birth Defects Prevention
Study (1997–2002)
Antidepressants
[42] Källén and Otterblad
Olausson, 2007
Sweden 495 40,728 N.A. population-based,
all births
Data from the nationwide Swedish Medical
Birth Register (1995–2004)
Anti-asthma medication (ß2-adrenergic
agonists, inhaled corticosteroids,
anticholinergic drugs, cromoglicic acid,
xanthines, leucotrien receptor antagonists)
[77] Källén, 2007 Sweden 11 873,383 < 20 - ≥45 population-based,
all births
Data from the nationwide Swedish Medical
Birth Register (1995–2004)
Folic acid
[64] Louik, 2007 USA 215 5860 N.A. population-based,
no birth defects
Data from the Slone Epidemiology Center
Birth Defects Study (1993–2004)
Antidepressants (any SSRI, fluoxetine,
sertraline, paroxetine, citalopram,
non-SSRI antidepressant)
[66] Czeizel, 2004 Hungary 220 38,151 < 25 - > 29 national-based,
no birth defects
Data from the Hungarian Congenital Abnormality
Registry (1980–1996) and National Birth Registry
of the Central Statistical Office (1996–1992)
Folic acid, multivitamins
[69] Czeizel, 2004 Hungary 220 38,151 < 25 - > 29 national-based,
no birth defects
Data from the Hungarian Congenital Abnormality
Registry (1980–1996) and National Birth Registry
of the Central Statistical Office (1996–1992)
Multivitamins
[6] Correa, 2003 USA 50 3029 < 20 - ≥30 population-based,
no birth defects
Data from the Atlanta Birth Defects Case-Control
Study (1968–1980)
Multivitamins
[65] Czeizel, 2003 Hungary 220 38,151 < 25 - > 29 national-based,
no birth defects
Data from the Hungarian Congenital Abnormality
Registry (1980–1996) and National Birth Registry
of the Central Statistical Office (1996–1992)
Diazepam
[78] Källén and Mottet,
2003
Sweden 8 504,660 < 19–45 population-based,
all births
Data from the nationwide Swedish Medical
Birth Register (1995–2001)
Meclozine
[43] Bonnot, 2001 France 6 13,703 N.A. population-based,
all births
Data from the French Central-East Registry of
congenital malformations (1976–1998)
Lorazepam
[70] Czeizel, 2001 Hungary 220 38,151 < 25 - > 29 national-based,
no birth defects
Data from the Hungarian Congenital Abnormality
Registry (1980–1996) and National Birth Registry
of the Central Statistical Office (1996–1992)
Cephalosporin (cephalexin, cefuroxime)
[51] Myers, 2001 USA 50 222,264 N.A. provinces-based,
all births
Data from a public health campaign conducted
in China (1993–1995)
Folic acid
[71] Czeizel, 2000 Hungary 220 38,151 < 25 - > 29 national-based,
no birth defects
Data from the Hungarian Congenital Abnormality
Registry (1980–1996) and National Birth Registry
of the Central Statistical Office (1996–1992)
Acetylsalicylic acid
[72] Stoll, 1997 France 108,
51c
108 F: mean age 26.9,
M: mean age 29.9
hospital-based,
no birth defects
Interview (1979–1995) Antibiotics, antispasmodics, estrogens and
other miscellaneous medication
[74] Angerpointer, 1981 Germany 78
78
78
78
210d
169e
75f
53g
< 20 - > 40 hospital-based,
other malformed infants
Questionnaire (1970–1974) Antiemetic, analgetic, laxative and
antihypotensive drugs, and iron preparations
[79] Heinonen, 1977 USA 13 N.A. N.A. population-based,
no controls
Data from the Collaborative Perinatal Project
(1958–1965)
Aspirin
  1. N.A. not available, SSRI selective serotonin reuptake inhibitors, EA/TEF esophageal atresia with or without tracheoesophageal fistula, ARM anorectal malformation
  2. aControl group included n = 98 patients with isolated EA/TEF and n = 42 patients with the combined phenotype of EA/TEF and ARM
  3. bIncluded 493 cases from the Netherlands and 150 cases from Germany
  4. cARM infants with isolated (no additional major defects) anomaly
  5. dControl group includes 41 infants with esophageal atresia, 41 with stenosis/atresia of the small and large bowel, 75 with Hirschsprung’s disease, 28 with omphalocele and 25 with gastroschisis
  6. eControl group includes 41 infants with esophageal atresia, 75 with Hirschsprung’s disease, 28 with omphalocele and 25 with gastroschisis
  7. fControl group includes 75 infants with Hirschsprung’s disease
  8. gControl group includes 28 infants with omphalocele and 25 with gastroschisis