Table 1.
Characteristics of cohort studies in the meta‐analysis
| First author (ref), year, location | Study period | No. of cohort/case | Outcomes | Risk estimates (95% CI) | Adjusted factors |
|---|---|---|---|---|---|
| Furu et al. 22 , 2015, Europe | 1996–2010 | 2 303 647 | Odds ratio | Maternal age, year of birth, birth order, smoking, maternal diabetes, country and use of other prescribed drugs. | |
| 26 854 | Any cardiac defects | 1.13 (0.93–1.38) | |||
| 17 573 | Atrial and ventricular septal defect | 1.05 (0.82–1.35) | |||
| 1079 | Atrioventricular septal defect | 1.81 (0.80–4.06) | |||
| 2231 | Conotruncal and major arch anomalies | 1.02 (0.48–2.15) | |||
| 2599 | Left ventricular outflow tract obstruction | 0.82 (0.37–1.84) | |||
| 2720 | Right ventricular outflow tract obstruction | 1.40 (0.81–2.42) | |||
| Berard et al. 21 , 2015, North America | 1998–2010 | 18 493 | Risk ratio | Maternal age, welfare status, other diabetes, hypertension, asthma, and medication use. | |
| 354 | Cardiac malformations | 1.16 (0.62–2.19) | |||
| 281 | Ventricular/ atrial septal defect | 1.34 (1.02–1.76) | |||
| 122 | Nervous system | 1.67 (0.68–4.13) | |||
| 87 | Eye, ear, face and neck | 0.46 (0.06–3.32) | |||
| 181 | Digestive system | 1.13 (0.46–2.77) | |||
| 164 | Genital organs | 0.97 (0.34–2.75) | |||
| 144 | Urinary system | 0.86 (0.27–2.72) | |||
| 635 | Musculoskeletal system | 1.04 (0.63–1.72) | |||
| Ban et al. 23 , 2014, Europe | 1990–2009 | 349 127 | Odds ratio | Maternal age at the end of pregnancy, year of childbirth, Townsend deprivation quintile, maternal smoking history, body mass index before pregnancy, and maternal diabetes, hypertension, asthma and epilepsy in the year before conception or during pregnancy. | |
| N/A | MCAs | 1.27 (0.85–1.89) | |||
| N/A | Specific heart anomalies | 1.52(0.78–2.96) | |||
| N/A | Genital system | 0.32 (0.04–2.40) | |||
| N/A | Urinary system | 0.54 (0.08–3.76) | |||
| N/A | Nervous system | 1.79 (0.42–7.54) | |||
| N/A | Musculoskeletal system | 2.13 (0.51–8.90) | |||
| N/A | Digestive system | 2.69 (0.67–10.76) | |||
| Huybrechts et al. 17 , 2014, North America | 2000–2007 | 949 504 | Odds ratio | N/A | |
| 6532 | Cardiac malformations | 1.27 (1.07–1.52) | |||
| 3275 | Ventricular septal defect | 1.24 (0.96–1.59) | |||
| 1062 | Right ventricular outflow tract obstruction | 1.03 (0.64–1.66) | |||
| 3280 | Other cardiac defect | 1.39 (1.10–1.76) | |||
| Jimenez‐Solem et al. 18 , 2012, Europe | 1997–2009 | 848 786 | Odds ratio | Mother's age, parity, income, education, smoking and year of conception. | |
| N/A | Congenital malformation of the heart | 2.73 (1.75–4.26) | |||
| N/A | Septal defects | 3.09 (1.82–5.25) | |||
| N/A | Ventricular septal defects | 3.60 (1.86–6.96) | |||
| N/A | Atriventricular septal defects | 2.85 (1.35–5.99) | |||
| N/A | Nervous system | 0.85 (0.12–6.07) | |||
| N/A | Eye | 1.05 (0.15–7.45) | |||
| N/A | Ear, face and neck | 6.13 (0.85–44.05) | |||
| N/A | Digestive system | 1.43 (0.36–5.74) | |||
| N/A | Internal urinary system | 0.44 (0.06–3.11) | |||
| N/A | External genital organs | 0.41 (0.06–2.93) | |||
| N/A | Musculoskeletal system | 0.83 (0.12–5.90) | |||
| Nordeng et al. 24 , 2012, Europe | 1999–2009 | 63 395 | Odds ratio | Maternal depression, maternal age at delivery, parity and use of psychotropic drugs during pregnancy. | |
| 542 | Cardiovasular malformation | 1.15 (0.16–8.28) | |||
| Colvin et al. 25 , 2011, Western Australia | 2002–2005 | 123 405 | Odds ratio | N/A | |
| 672 | Cardiovascular anomalies | 1.74 (0.96–3.17) | |||
| N/A | Ventricular septal defect | 0.49 (0.07–3.50) | |||
| 289–294 | Nervous system | 1.08 (0.35–3.38) | |||
| 224–229 | Ear, face and neck | 0.46 (0.07–3.31) | |||
| 1330 | Urogenital system | 1.27 (0.07–2.09) | |||
| 539 | Digestive system | 0.97 (0.40–2.36) | |||
| 1059 | Musculoskeletal system | 0.69 (0.33–1.46) | |||
| Malm et al. 26 , 2011, Europe | 1996–2006 | 635 583 | Odds ratio | Maternal age at the end of pregnancy, parity, year of pregnancy ending, marital status, smoking any time during pregnancy, other reimbursed psychiatric drug purchases and entitlement for special reimbursement for prepregnancy diabetes. | |
| 8146 | All major cardiovascular anomalies | 0.65 (0.34–1.25) | |||
| 1281 | Atrial septal defect | 0.93 (0.23–3.76) | |||
| 5470 | Ventricular septal defect | 0.53 (0.22–1.29) | |||
| 435 | Conotruncal heart defect | 1.27 (0.18–9.15) | |||
| 239 | Transposition of great arteries | 2.55 (0.35–18.62) | |||
| N/A | Central nervous system | 1.35 (0.50–3.64) | |||
| N/A | Digestive system | 1.09 (0.35–3.41) | |||
| N/A | Urogenital system | 1.22 (0.55–2.74) | |||
| N/A | Musculoskeletal system | 0.97 (0.50–1.88) | |||
| Kornum et al. 19 , 2010, Europe | 1991–2007 | 216 042 | Odds ratio | Maternal smoking status, maternal age, birth order and birth year. | |
| 1410 | Cardiac malformations | 3.0 (1.4–6.4) | |||
| N/A | Septal heart defect | 3.3 (1.5–7.5) | |||
| Merlob et al. 20 , 2009, Israel | 2000–2007 | 67 871 | Relative risk | N/A | |
| 1084 | Congenital heart malformation | 8.78 (1.08–71.42) | |||
| Oberlander et al. 27 , 2008, North America | 1998–2001 | 11 957 | Odds ratio | N/A | |
| 515 | Cardiovascular congenital defects | 1.03 (0.33–3.23) | |||
| Kallen et al. 28 , 2007, Europe | 1995–2004 | 880 431 | Odds ratio | Year of birth, maternal age, parity, smoking and ≥3 previous miscarriages. | |
| 11 384 | Any cardiac defect | 0.76 (0.47–1.23) | |||
| 7174 | VSD and/or ASD | 1.06 (0.63–1.77) | |||
| 1218 | Unspecified cardiac defect | 0.55 (0.01–3.06) |
CI, confidence interval; ASD, atrial septal defect; MCA, major congenital anomalies; N/A, not available; VSD, ventricular septal defect