Table 2.
Quantitative synthesis of eligible positive associations for specific factor and subtypes of CHD
| Factor | Studies | Cases | Egger test | Random-effect | 95%PI | heterogeneity | excess significance bias | Fixed-effect | Random-effect | Gradea |
|---|---|---|---|---|---|---|---|---|---|---|
| p value | summary effect size(95%CI) | I2(%) | p value | p value | p value | |||||
| ASD | ||||||||||
| SSRIs (in the first trimester) | 6 | 6608 | 0.79 | 2.06 (1.40,3.02) | (0.68,6.23) | 57.77 | 0.97 | 6.33E-10 | 2.21E-04 | III |
| Maternal obesity | 4 | 2328 | 0.27 | 1.38 (1.21,1.59) | (0.87,2.19) | 28.15 | 0.71 | 5.98E-10 | 2.98E-06 | III |
| Fever | 6 | 2141 | 0.53 | 1.43 (1.01,2.39) | (0.37,5.55) | 40.76 | 0.94 | 4.41E-02 | 3.00E-03 | IV |
| SSRIs | 7 | 2967 | 0.50 | 1.82 (1.24,2.68) | (0.56,5.92) | 71.98 | 0.99 | 8.52E-08 | 2.37E-03 | IV |
| Maternal active smoking | 9 | 52,077 | 0.71 | 1.26 (1.02,1.61) | (0.59,2.72) | 73.23 | 0.03 | 4.19E-09 | 3.93E-02 | IV |
| Maternal severe obesity | 3 | 90 | 0.39 | 1.72 (1.35,2.19) | (0.15,19.48) | 46.79 | 0.00 | 3.35E-09 | 1.12E-05 | IV |
| Maternal moderate obesity | 3 | 346 | 0.45 | 1.26 (1.14,1.41) | (0.63,2.52) | 0.00 | 0.07 | 1.79E-05 | 1.79E-05 | IV |
| HLHS | ||||||||||
| Nitrofurantoin (in the first trimester) | 3 | 2845 | 0.22 | 3.07 (1.59,5.93) | (0.04,217.94) | 0.00 | 0.73 | 8.25E-04 | 8.25E-04 | III |
| Ondansetro | 3 | 28,777 | 0.72 | 1.49 (1.03,2.17) | (0.13,16.79) | 0.00 | 1.00 | 3.48E-02 | 3.48E-02 | IV |
| Maternal obesity | 4 | 146 | 0.17 | 1.52 (1.23,1.88) | (0.96,2.42) | 0.00 | 0.42 | 9.15E-05 | 9.15E-05 | IV |
| Maternal severe obesity | 3 | 32 | 0.22 | 1.60 (1.11,2.31) | (0.15,17.43) | 0.00 | 1.00 | 1.26E-02 | 1.26E-02 | IV |
| Maternal moderate obesity | 3 | 92 | 0.28 | 1.54 (1.21,1.95) | (0.33,7.11) | 0.00 | 0.18 | 3.51E-04 | 3.51E-04 | IV |
| Maternal overweight | 4 | 148 | 0.00 | 1.31 (1.08,1.60) | (0.85,2.03) | 0.00 | 1.00 | 7.18E-03 | 7.18E-03 | IV |
| ASD/VSD | ||||||||||
| SSRIs (in the first trimester) | 16 | 31,414 | 0.15 | 1.29 (1.14,1.45) | (0.91,1.81) | 41.86 | 0.18 | 1.08E-09 | 3.62E-05 | III |
| Septal defects | ||||||||||
| Sertraline | 3 | 1428 | 0.32 | 3.17 (2.11,4.76) | (0.23,43.91) | 0.00 | 0.36 | 2.40E-08 | 2.40E-08 | II |
| SSRIs | 6 | 7722 | 0.62 | 1.38 (1.02,1.86) | (0.56,3.42) | 67.14 | 0.98 | 4.76E-05 | 3.46E-02 | IV |
| Fluconazole (in the first trimester) | 3 | 42,838 | 0.22 | 1.43 (1.06,1.93) | (0.10,19.66) | 0.00 | 0.14 | 3.57E-03 | 1.98E-02 | IV |
| Maternal obesity | 4 | 3483 | 0.09 | 1.28 (1.03,1.59) | (0.63,2.59) | 9.27 | 0.74 | 8.66E-05 | 2.91E-02 | IV |
| TOF | ||||||||||
| GDM | 4 | 1696 | 0.60 | 1.51 (1.10,2.05) | (0.76,2.98) | 0.00 | 0.33 | 9.92E-03 | 9.92E-03 | IV |
| Maternal obesity | 5 | 887 | 0.48 | 1.28 (1.09,1.51) | (0.99,1.66) | 10.44 | 0.05 | 2.11E-03 | 2.11E-03 | IV |
| Maternal severe obesity | 3 | 648 | 0.14 | 1.95 (1.50,2.52) | (0.36,10.44) | 0.00 | 0.59 | 4.54E-07 | 4.54E-07 | IV |
| RVOTO | ||||||||||
| Fever | 3 | 2020 | 0.31 | 1.66 (1.04,2.63) | (0.01,229.96) | 60.41 | 0.06 | 2.64E-03 | 3.22E-02 | IV |
| SSRIs | 4 | 4318 | 0.34 | 1.39 (1.09,1.77) | (0.61,3.16) | 32.18 | 0.94 | 5.80E-04 | 8.45E-03 | IV |
| Maternal active smoking | 3 | 30,993 | 0.14 | 1.43 (1.03,1.99) | (0.07,28.91) | 24.71 | 0.89 | 6.03E-03 | 3.11E-02 | IV |
| COA | ||||||||||
| Maternal obesity | 4 | 534 | 0.36 | 1.25 (1.02,1.52) | (0.80,1.94) | 0.00 | 1.00 | 3.02E-02 | 3.02E-02 | IV |
| Maternal moderate obesity | 3 | 502 | 0.62 | 1.29 (1.03,1.60) | (0.31,5.36) | 0.00 | 1.00 | 2.42E-02 | 2.42E-02 | IV |
| CTD | ||||||||||
| Fever | 4 | 2560 | 0.54 | 1.40 (1.01,2.02) | (0.47,4.18) | 5.41 | 0.96 | 4.26E-02 | 3.68E-02 | IV |
| Maternal obesity | 3 | 1278 | 0.12 | 1.23 (1.08,1.40) | (0.52,2.88) | 0.00 | 0.67 | 2.37E-03 | 2.37E-03 | IV |
| OFT | ||||||||||
| Maternal obesity | 3 | 620 | 0.79 | 1.39 (1.25,1.55) | (0.62,3.15) | 0.00 | 0.62 | 2.66E-11 | 8.89E-10 | IV |
| Maternal overweight | 3 | 998 | 0.14 | 1.19 (1.09,1.31) | (0.57,2.78) | 0.00 | 0.17 | 1.50E-4 | 1.50E-4 | IV |
| TGA | ||||||||||
| Fever | 4 | 1016 | 0.43 | 1.85 (1.11,3.09) | (0.48,7.12) | 0.00 | 0.96 | 1.22E-02 | 1.85E-02 | IV |
| VSD | ||||||||||
| Gestational hypertension | 4 | 32,978 | 0.00 | 1.29 (1.17,1.43) | (1.03,1.61) | 58.06 | 0.03 | 7.84E-07 | 7.84E-07 | II |
| Maternal severe obesity | 3 | 424 | 0.41 | 1.09 (1.02,1.69) | (0.04,30.31) | 14.99 | 1.00 | 7.04E-01 | 3.92E-02 | IV |
| AVSD | ||||||||||
| Maternal severe obesity | 3 | 756 | 0.37 | 1.44 (1.03,2.00) | (0.17,12.39) | 0.00 | 1.00 | 3.23E-02 | 3.23E-02 | IV |
aIoannidis’s five-class evidence grade
Abbreviation: CI Confidence interval, PI Predictive interval, IVF In-vitro-fertilization, ICSI Intracytoplasmic sperm injection, SSRI Selective serotonin reuptake inhibitor, SNRI serotonin-norepinephrine reuptake inhibitor, DM maternal diabetes mellitus, PGDM pregestational diabetes mellitus, GDM gestational diabetes mellitus, TTTS twin–twin transfusion syndrome, MC Monochorionic, ASD Atrial septal defect, HLHS Hypoplastic left heart syndrome, VSD Ventricular septal defects, TOF Tetralogy of fallot, RVOTD Right ventricular outflow tract obstruction, COA Coarctation of the aorta, CTD Conotruncal defects, OFT outflow tract, TGA Transposition of great arteries, AVSD Atrioventricular septal defect