Table 2. Summary associations between maternal obesity and CHDs.
| Summary associations: OR unless otherwise specified (95% CI) | No. of studies (Offspring if reported) | Model: FE or RE, adjustment | Heterogeneity: χ2 I2 (%) | |
| Obesity (BMI>30 kg/m2) (referent BMI 18.5–24.9 kg/m²) | ||||
| Stothard (2009), weight assessment pre-pregnancy or early pregnancy | ||||
| Studies overall | 1.30 (1.12 to 1.51) | 7 (638, 983) | RE, none | I2 58 |
| Adjusted | 1.27 (1.11 to 1.46) | 3 | RE, NR | NR |
| Higher quality* | 1.51 (1.19 to 1.93) | 2 | RE, none | NR |
| Excluding chromosomal anomalies | 1.36 (1.16 to 1.59) | 6 | RE, none | NR |
| Excluding PDM | 1.35 (1.11 to 1.64) | 4 | RE, none | NR |
| Including terminations | 1.51 (1.19 to 1.93) | 2 | RE, none | NR |
| Objective BMI measure | 1.25 (0.94 to 1.65) | 2 | RE, none | NR |
| Cai (2014), weight assessment pre-pregnancy or early pregnancy | ||||
| Studies overall | 1.23 (1.19 to 1.27) | 13 (770, 251) | FE, none | I2 49 |
| Excluding PDM, included GDM | 1.28 (1.18 to 1.39) | 5 | RE, none | NR |
| Excluding PDM and GDM | 1.16 (1.08 to 1.23) | 4 | RE, none | NR |
| From the USA | 1.25 (1.20 to 1.30) | 7 | FE, none | NR |
| From other countries | 1.16 (1.09 to 1.25) | 6 | FE, none | NR |
| Live births, stillbirths, terminations | 1.31 (1.18 to 1.46) | 4 | FE, none | NR |
| Liveborn or newborn infants | 1.29 (1.07 to 1.99) | 7 | RE, none | NR |
| Zhu (2018), weight assessment maternal, not further specified | ||||
| Studies overall | 1.17 (1.14 to 1.20) | 17 | FE, NR | I2 25.5 |
| USA | 1.17 (1.14 to 1.20) | 11 | FE, NR | I2 43 |
| Not the USA | 1.17 (1.10 to 1.25) | 6 | FE, NR | I2 0 |
| Published 2010 and earlier | 1.18 (1.12 to 1.24) | 9 | FE, NR | I2 24 |
| Published after 2010 | 1.17 (1.14 to 1.20) | 8 | FE, NR | I2 34 |
| Case control | 1.17 (1.14 to 1.21) | 13 | FE, NR | I2 38 |
| Cohort study | 1.16 (1.10 to 1.22) | 4 | FE, NR | I2 0 |
| NOS score <7 | 1.17 (1.13 to 1.21) | 5 | FE, NR | I2 37 |
| NOS score ≥7 | 1.17 (1.13 to 1.21) | 12 | FE, NR | I2 26 |
| Zheng (2018), weight assessment prepregnancy or in early pregnancy† | ||||
| Studies overall | 1.32 (1.21 to 1.43) | 20 | RE, 5 none; 15 adjusted or matched, variables NR | I2 62 |
| North America | 1.31 (1.14 to 1.50) | 7 | NR | I2 69 |
| Europe | 1.23 (1.13 to 1.34) | 6 | NR | I2 50 |
| Asia | 1.94 (1.16 to 3.22) | 6 | NR | I2 49 |
| Oceania | 1.34 (0.63 to 2.85) | 1 | NR | NA |
| Hospital-based sample | 1.71 (1.24 to 2.34) | 9 | NR | I2 54 |
| Population-based sample | 1.26 (1.17 to 1.35) | 11 | NR | I2 62 |
| Live births only | 1.35 (1.19 to 1.54) | 9 | NR | I2 71 |
| Live births, stillbirths and or termination | 1.37 (1.18 to 1.59) | 10 | NR | I2 21 |
| Case controls | 1.40 (1.23 to 1.61) | 14 | NR | I2 59 |
| Cohort studies | 1.28 (1.13 to 1.47) | 6 | NR | I2 72 |
| Singletons | 1.40 (1.23 to 1.61) | 7 | NR | I2 39 |
| Singletons and multiples | 1.28 (1.13 to 1.47) | 4 | NR | I2 80 |
| BMI assessed prepregnancy | 1.44 (1.23 to 1.68) | 16 | NR | I2 56 |
| BMI assessed early pregnancy | 1.28 (1.16 to 1.42) | 4 | NR | I2 81 |
| Adjustment or matching | 1.37 (1.22 to 1.54) | 15 | NR | I2 67 |
| No adjustment | 1.25 (1.06 to 1.49) | 5 | NR | I2 20 |
| Higher quality‡ | 1.30 (1.20 to 1.40) | 17 | NR | I2 61 |
| Lower quality | 2.18 (0.91 to 5.21) | 3 | NR | I2 63 |
| Excl. PGDM and GDM | 1.23 (0.96 to 1.57) | 4 | NR | I2 34 |
| PDM/GDM not excluded | 1.36 (1.23 to 1.50) | 8 | NR | I2 65 |
| Liu (2019) (RR) (level I evidence), weight assessment prepregnancy or early pregnancy | ||||
| Studies overall | 1.23 (1.17 to 1.29) | 19 | RE, Varied§ | I2 48 |
| Cohort studies | 1.22 (1.15 to 1.31) | 6 | RE, NR | I2 53 |
| Case controls | 1.24 (1.15 to 1.33) | 13 | RE, NR | I2 48 |
| USA | 1.24 (1.15 to 1.32) | 12 | RE, NR | I2 48 |
| Not the USA | 1.22 (1.14 to 1.32) | 7 | RE, NR | I2 52 |
| Sample size <10 000 | 1.27 (1.08 to 1.49) | 10 | RE, NR | I2 49 |
| Sample size ≥10 000 | 1.21 (1.16 to 1.26) | 9 | RE, NR | I2 38 |
| Adjusted for maternal age | 1.24 (1.17 to 1.31) | 8 | RE, NR | I2 54 |
| Not adjusted for maternal age | 1.20 (1.08 to 1.33) | 11 | RE, NR | I2 47 |
| Adjusted for maternal smoking | 1.24 (1.17 to 1.31) | 7 | RE, NR | I2 58 |
| Not adjusted for maternal smoking | 1.20 (1.09 to 1.33) | 12 | RE, NR | I2 42 |
| Adjusted for maternal education | 1.24 (1.17 to 1.33) | 6 | RE, NR | I2 62 |
| Not adjusted for maternal education | 1.21 (1.11 to 1.31) | 13 | RE, NR | I2 38 |
| Wu (2023) | ||||
| Studies overall | 1.29 (1.22 to 1.37) | 23 | RE, 16 adjusted, varied¶ | I2 47 |
| Cohort studies | 1.36 (1.23 to 1.50) | NR | RE | I2 30 |
| Case controls | 1.27 (1.19 to 1.35) | NR | RE | I2 41 |
| Adjusted | 1.27 (1.19 to 1.35) | NR | RE | I2 54 |
| Not adjusted | 1.44 (1.26 to 1.65) | NR | RE | I2 0 |
| Moderate obesity (BMI 30.1–34.9 or 30.1–39.9 kg/m2) (referent BMI 18.5–24.9 kg/m²) | ||||
| Cai (2014), weight assessment pre-pregnancy or early pregnancy | ||||
| Studies overall | 1.15 (1.11 to 1.20) | 5 (735, 281) | FE, none | I2 35 |
| >500 infants | 1.16 (1.11 to 1.21) | 4 | FE, none | NR |
| Excl. PGDM, including GDM | 1.17 (1.12 to 1.23) | 3 | FE, none | NR |
| Excluded PGDM and GDM | 1.12 (1.04 to 1.20) | 2 | FE, none | NR |
| From the USA | 1.17 (1.12 to 1.23) | 3 | FE, none | NR |
| From other countries | 0.99 (0.72 to 1.37) | 2 | FE, none | NR |
| Liveborn infants or newborn infants | 1.14 (1.07 to 1.22) | 4 | FE, none | NR |
| Zheng (2018), weight assessment prepregnancy or early pregnancy | ||||
| Studies overall | 1.15 (1.11 to 1.20) | 2 | FE, both studies adjusted, variables NR | I2 0 |
| Class II obesity (BMI 35 to <40 kg/m2) (referent BMI 18.5–24.9 kg/m²) | ||||
| Zheng (2018) (level I evidence), weight assessment prepregnancy or early pregnancy | ||||
| Studies overall | 1.26 (1.18 to 1.34) | 2 | FE, both studies adjusted, variables NR | I2 0.91 |
| Class III obesity (BMI≥40 kg/m2) prepregnancy or in early pregnancy (referent BMI 18.5–24.9 kg/m²) | ||||
| Zheng (2018)40 (level I evidence) | ||||
| Studies overall | 1.42 (1.33 to 1.51) | 5 | FE, all studies adjusted or matched, variables NR | I2 0 |
| Severe obesity (BMI≥35.0 or ≥40 kg/m2) (referent BMI 18.5–24.9 kg/m²) | ||||
| Cai (2014), weight assessment prepregnancy or early pregnancy | ||||
| Studies overall | 1.39 (1.31 to 1.47) | 5 (665, 528) | FE, none | I2 49 |
| >500 infants | 1.44 (1.34 to 1.54) | 4 | ||
| Excluded PGDM, included GDM | 1.46 (1.35 to 1.58) | 3 | FE, none | NR |
| Excluded PGDM and GDM | 1.38 (1.20 to 1.59) | 2 | FE, none | NR |
| From the USA | 1.45 (1.34 to 1.57) | 3 | FE, none | NR |
| From other countries | 1.39 (1.21 to 1.61) | 2 | FE, none | NR |
| Liveborn infants or newborn infants | 1.38 (1.30 to 1.47) | 3 | FE, none | NR |
Defined as excluded chromosomal anomalies and pregestational diabetes and included terminations.
Subgroup analysis considered potential modification of associations seen in the overall analysis by the characteristics reported in the table above (ie, region; live birth, stillbirth terminations; design; plurality; timing of BMI assessment; adjustment; study quality; exclusion of participants with diabetes), and no differences were detected.
Defined as NOS overall score ≥7.
included site, maternal age, race, insurance, maternal smoking, education, hypertension, parity, folic acid supplementation use, gestational diabetes, maternal alcohol use, PGDM, maternal height, early pregnancy, maternal country of birth, family situation, sex of offspring, payment method for healthcare, index of multiple deprivation, ethnicity, birth period, chronic illness, and none.
included race, birth period, age, education, alcohol use, smoking, chronic illness, vitamin use, parity, ethnicity, smoking in the month prior to conception, folic acid supplementation in the month prior to conception, pregestational diabetes (1 study only), any cigarette smoking during pregnancy, index of multiple deprivation, infant gender, BMI, any alcohol consumption, dietary folic intake, caffeine intake, family history of a heart defect, residence of mother, any vitamin use. Gestational diabetes (1 study), any diabetes (1 study), urban/rural status, paternal age, family history of congenital anomalies, and none (7 studies).
BMIbody mass indexCHDscongenital heart defectsFEfixed effectGDMgestational diabetes mellitusNOSNewcastle-Ottawa ScaleNRnot reportedPGDMpregestational diabetes mellitusRErandom effect