While infant deaths associated with congenital heart defects have declined substantially over the past 2 decades, congenital heart disease remains the most common fatal congenital anomaly in the first year after birth.
Prematurity is the most significant cause of death in the first week of life, but after that point, birth defects take over as the leading cause of infant mortality (and overall, birth defects are the leading cause of infant mortality). Cardiovascular defects, in turn, are the single largest contributor to infant mortality attributable to birth defects – severe congenital heart disease (CHD) affects approximately 0.5% of all neonates and is responsible for one-third of deaths between birth and 1 year of life.
Prenatal diagnosis of CHD is important because early detection can improve the planning of services and provision of coordinated multidisciplinary care. While most fetal therapy for CHD is investigational and still evolving, studies from all over the world have shown that if a baby is known to have a heart problem and is delivered at a facility that provides definitive care, the baby will likely fare better.
Unfortunately, most infants born with CHD do not have defined risk factors. As obstetricians we must always be alert to the possibility that, even without a clear risk factor, there could be a cardiovascular problem.
It is important to know, on the other hand, who is at increased risk and should be evaluated further, and who is not at increased risk. We know now that certain infants whom we haven't traditionally thought of as being at risk for CHD are indeed at higher risk. Our knowledge of familial contributions to CHD has grown, for instance, giving obstetricians the responsibility to be alert for potential familial genetic patterns so that the proper counseling can be provided.
There are also noninherited risk factors that can be identified and potentially modified. It is unclear what proportion of CHD can be prevented, but at the least, obstetricians should be aware of such risk factors so they can provide guidance to parents and future parents that could reduce the risk of their children having a major cardiovascular malformation, and so they can ensure proper surveillance in any pregnancy.
Over the past 15 years or so, our understanding of inherited causes of congenital heart defects has increased significantly, and while there is much more to learn, it is now appreciated that genetics plays a greater role in CHD than previously estimated.
Molecular genetics studies in families with multiple affected individuals have even led to the identification of specific genetic abnormalities for several forms of CHD, such as the single gene mutation sometimes seen in tetralogy of Fallot; others are related to mutations in more than one gene.
While most chromosome defects are not inherited, some anomalies or syndromes with cardiac phenotypes – for instance, those involving microdeletions or gonadal mosaicism – can be inherited and play a small but increasingly appreciated role in CHD. The William-Beuren syndrome and the 22q11.2 deletion syndrome, for instance, are microdeletion syndromes that show autosomal dominant inheritance.
Overall, parents of a child with CHD that is not associated with a typical chromosomal aberration have a 2%–3% chance of having another child with CHD; it is estimated that half of affected siblings will be diagnosed with the same lesion, the other half with a different lesion.
Classic Mendelian transmission is occasionally responsible for inherited CHD in families, but recurrence risk is significant only when the family history of CHD involves first- or second-degree relatives.
Fetal echocardiography is definitely warranted when the mother or father – or a sibling – of the fetus has CHD, as well as when CHD has affected a parent's own mother, father, sister, or brother.
Once you get further out in the family history, to cousins and other third-degree and more distant relatives, the risk is not high enough to warrant a more detailed fetal examination. This is important for counseling; parents who are worried about a history of CHD in third-degree relatives should be reassured.
Among the changes in patterns of referral for fetal echocardiography that we detected at Yale-New Haven Hospital from 1985 to 2003 was an 18% increase in referrals for a family history of CHD, including family history in more distant relatives.
This increase was not accompanied by any change in the percentage of structural cardiovascular heart defects consequently detected (J. Ultrasound Med. 2006;25:197-202).
As an increasing number of patients with major congenital cardiac defects have been surviving to adulthood and parenthood, numerous investigators have attempted to identify specific recurrence risks.