Risks of specific congenital anomalies in offspring of mothers with preexisting diabetes

Outcome	Number of events	Pre-gestational diabetes
Outcome	Number of events	Number of studies	Pooled RR (95% CI)	I² (%)	P value
Heterotaxia	1098	4	8.78 (6.66 to 11.56)	0.0	0.423
Conotruncal defects	5495	4	3.76 (2.58 to 5.48)	68.3	0.024
Truncus arteriosus	435	3	12.16 (7.52 to 19.68)	0.0	0.866
Transposition of great vessels	6700	9	3.25 (2.54 to 4.15)	15.9	0.301
Tetralogy of fallot	5360	6	3.46 (2.27 to 5.28)	64.4	0.015
APVR	1239	4	3.47 (2.13 to 5.64)	0.0	0.684
LVOT defects	6672	7	3.46 (2.59 to 4.62)	37.8	0.140
Coarctation of aorta	6606	5	3.35 (2.25 to 4.99)	61.4	0.035
Hypoplastic left heart	2319	4	2.23 (1.07 to 4.64)	64.0	0.040
RVOT defects	6163	7	3.41 (2.65 to 4.38)	20.9	0.270
Pulmonary artery anomalies	17,215	3	2.81 (2.48 to 3.18)	0.0	0.865
Pulmonary valve stenosis	7273	5	2.51 (1.51 to 4.17)	76.2	0.002
Septal defects	12,368	2	3.23 (2.20 to 4.74)	86.2	0.007
AVSD	5126	6	3.94 (2.95 to 5.26)	40.0	0.139
VSD	64,844	10	3.10 (2.32 to 4.16)	90.2	<0.001
ASD	91,683	7	3.12 (2.42 to 4.02)	81.9	<0.001
VSD + ASD	1089	2	6.36 (4.38 to 9.24)	0.0	0.527
Single ventricle	1228	4	5.91 (2.43 to 14.38)	80.2	0.002
Nervous system defects	42,339	9	2.54 (1.73 to 3.73)	94.8	<0.001
Neural tube defects	8791	6	2.74 (1.46 to 5.14)	75.5	0.001
Anencephaly	3859	3	2.72 (2.16 to 3.44)	0.0	0.416
Encephalocele	1108	3	5.53 (3.24 to 9.45)	52.8	0.120
Spina bifida	9948	8	1.89 (1.15 to 3.09)	71.1	0.001
Hydrocephaly	10,733	5	3.46 (1.62 to 7.42)	85.0	<0.001
Holoprosencephaly	301	2	18.18 (4.03 to 82.06)	66.3	0.085
Eye, ear, face, and neck defects	39,570	6	3.14 (2.90 to 3.39)	0.0	0.444
Orofacial clefts	6,602	5	1.27 (0.54 to 2.98)	90.4	<0.001
Cleft palate	11,259	6	1.75 (1.04 to 2.94)	74.6	0.001
Cleft lip with or without cleft palate	32,641	7	1.89 (1.22 to 2.92)	81.1	<0.001
Digestive system defects	14,286	7	2.02 (1.24 to 3.28)	92.3	<0.001
Diaphragmatic hernia	5882	3	1.66 (1.32 to 2.10)	0.0	0.520
Abdominal wall defects	1691	2	1.31 (0.80 to 2.15)	0.0	0.729
Omphalocele	4163	3	1.90 (1.48 to 2.44)	0.0	0.447
Gastroschisis	9268	3	0.92 (0.68 to 1.24)	0.0	0.399
Genitourinary system defects	128,657	10	1.73 (1.35 to 2.21)	89.2	<0.001
Renal agenesis/dysgenesis	5239	6	5.63 (2.48 to 12.76)	86.1	<0.001
Hypospadias	44,963	9	1.57 (1.22 to 2.02)	74.1	<0.001
CAKUT	4143	3	1.80 (1.41 to 2.30)	0.0	0.865
Musculoskeletal system defects	123,365	11	1.98 (1.45 to 2.72)	94.4	<0.001
Limb reduction	23,963	9	2.73 (1.98 to 3.76)	81.7	<0.001
Polydactyly/syndactyly	20,328	4	0.95 (0.57 to 1.57)	71.8	0.003
Multiple congenital anomalies	2448	5	3.06 (2.36 to 3.96)	39.6	0.158
Major congenital anomalies	52,171	6	2.14 (1.65 to 2.77)	81.8	<0.001

Rates (95% CI) of major groups and selected subtypes of congenital anomalies* in pregnancies of women with and without pre-existing diabetes per 1000 singleton pregnancies and relative risk (95% CI).

APVR: anomalous pulmonary venous return; ASD: atrial septal defect; AVSD: atrioventricular septal defect; CAKUT: congenital anomalies of the kidney and urinary tract; CHD: congenital heart defect; CI: confidence interval; LVOT: left ventricular outflow tract; RR: relative risk; RVOT: right ventricular outflow tract; VSD: ventricular septal defect.
* European Surveillance of Congenital Anomalies (EUROCAT) coding.

Adapted from: Zhang TN, Huang XM, Zhao XY, et al. Risks of specific congenital anomalies in offspring of women with diabetes: A systematic review and meta-analysis of population-based studies including over 80 million births. PLoS Med 2022; 19:e1003900. Copyright © The Authors. Available at: https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003900 (Accessed on March 18, 2021). Adapted under the terms of the Creative Commons Attribution License 4.0.

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Risks of specific congenital anomalies in offspring of mothers with preexisting diabetes