Personal history
History of acute rheumatic fever, multisystem inflammatory syndrome in children, or Kawasaki disease
Family history
Congenital heart disease	Depending on etiology, high rates within families, with siblings having increased risk of 3 to 24 times higher than the general population
Hypertrophic cardiomyopathy	Depending on etiology, first-degree relatives should generally have an echocardiography screening
Sudden unexplained death	Could be a sign of undiagnosed congenital heart disease or a genetic cardiomyopathy
Genetic syndrome/association/sequence
Aneuploidy	Trisomy 21 associated with a variety of cardiac pathologies (endocardial cushion-related pathology)
	Turner syndrome associated with aortic valve and root anomalies
Connective tissue pathologies	Marfan syndrome associated with aortic aneurysm and root dilatation
≥ 3 minor structural anomalies or one major anomaly	3 minor anomalies carry a 90% risk of a major anomaly, including structural heart disease in conditions such as Noonan syndrome, Pierre Robin sequence, osteogenesis imperfecta, VACTERL association, CATCH 22 syndrome, CHARGE syndrome, and others
Inborn errors of metabolism or lysosomal storage diseases	Common comorbidities include aortic and mitral valve disease, depending on the exact disease; phenylketonuria is strongly associated with congenital heart disease
Exposure to teratogenic medications
Lithium, valproic acid and other antiepileptic drugs; mycophenolate mofetil (Cellcept), warfarin (Coumadin), angiotensin-converting enzyme inhibitors, retinoic acid, vitamin A derivatives (not topical)	U.S. Food and Drug Administration labeling contains prevalence and extent of associations that vary for each medication
Nonsteroidal anti-inflammatory drugs	Third trimester exposures associated with an odds ratio of 15 for premature closure of the ductus arteriosus
Prenatal factors
First-trimester maternal infections	Conotruncal (lesions that lead to abnormal ventriculo-arterial alignment) and obstructive defects are more likely; rubella is associated with persistent ductus arteriosus and pulmonary artery stenosis
Maternal diabetes mellitus (especially preexisting diabetes)	3% to 5% of infants of patients who have diabetes and aortic, vascular, or endocardial problems
Maternal obesity	Prevalence rate ratios of aortic arch defects and transposition of the great arteries were doubled in offspring of patients with a body mass index > 40 kg per m2; atrial septal defects and persistent ductus arteriosus prevalence rate ratio increase with maternal body mass index
Prenatal diagnostics	Any diagnostic concern based on prenatal sonography of the heart (intracardiac foci in isolation do not constitute a concern)