We've also known for some time that differences in CHD may exist even with good metabolic control. Studies have documented mild cardiac hypertrophy involving the interventricular septum and the ventricular free walls, for instance, in diabetic mothers with good metabolic control (J. Pediatr. 1991;118:103-7 and Am J. Obstet. Gynecol. 1991;164:837-43). Such growth affects cardiac diastolic function.
With the epidemic of obesity and the increasing prevalence of early type 2 diabetes and glucose intolerance among women of childbearing age, however, this is an increasingly important risk factor to appreciate and counsel about.
The most important message, we've learned, is that there's no such thing as perfect control – that good metabolic control will not necessarily protect diabetic mothers from the higher risk of CHD.
Just as detection and appropriate management of diabetes before and during pregnancy are of utmost importance, so is fetal echocardiography for every pregnant woman who has pregestational diabetes – even diabetes that is well controlled.
Indeed, the same review of all fetal echocardiography performed between 1985 and 2003 at Yale-New Haven Hospital that showed an increase in referrals for family history also showed a 9% increase in the proportion of studies done for pregestational diabetes as the indication. The increase was most striking when it came to women who had recently been diagnosed, compared with long-standing diabetes – a finding that likely reflects the increase in obesity.
▸ Phenylketonuria. Fortunately, strict dietary control before conception and during pregnancy can reduce the increased risk of heart defects faced by women with this disorder. We need to remember that aspartame (NutraSweet) can cause phenylalanine levels to increase in women with PKU, but not in normal women. Women without PKU can be reassured that there is no evidence linking aspartame with birth defects.
Fetal Risks
Among the fetal risk factors important to consider are:
▸ Extracardiac anomalies. The identification of any extracardiac anomaly should raise our level of suspicion for other anomalies, including congenital heart defects. If we see one anomaly – anywhere in the fetus – there often are really two. And if we see two anomalies, there frequently are really three.
▸ Nonimmune hydrops. All fetuses found to have NIH should be evaluated with fetal echocardiography. Structural heart disease in fetuses with NIH is usually indicative of a poor prognosis for survival, but when rhythm disturbances/arrhythmias are detected in association with NIH, there is sometimes an option for prenatal treatment.
▸ Fetal arrhythmias. An irregular heartbeat is usually not a problem, but tachycardia and especially bradycardia are associated with an increased risk of CHD. There may be structural heart defects in as many as half of fetuses with fixed bradycardia (i.e., baseline heart rate less than 100). In general, it is best that all arrhythmias are examined; it is just too hard to tell them apart by auscultation alone.
▸ Nuchal translucency. Numerous studies have shown that elevated first-trimester nuchal translucency (NT) increases the risk of major congenital heart defects in chromosomally normal fetuses, and that risk increases with increasing NT measurement.
In a large prospective multicenter study conducted by the National Institute of Child Health and Human Development, for instance, investigators identified 21 cases of major congenital heart defects in 8,167 chromosomally normal pregnancies. They reported that the incidence of CHD per 1,000 pregnancies rose from 1.9 with an NT measurement of less than 2.0 mm, to 4.8 with an NT measurement of 2.0–2.4 mm, to 6.0 with an NT measurement of 2.5–3.4 mm, to 23 of every 1,000 pregnancies with an NT measurement of 3.5 mm or greater (Am. J. Obstet. Gynecol. 2005;192:1357–61).
If the NT is greater than 3.5 mm, measured by a qualified sonographer or sonologist at 11–14 weeks as part of an aneuploidy risk assessment scan, the patient should be referred for fetal echocardiography.
▸ In vitro fertilization. We recently investigated the prevalence of congenital heart defects among IVF pregnancies at our referral program at Yale, and found that children conceived through IVF were 3–12 times as likely to have CHD as was the general population (J. Ultrasound Med. 2010;29:917-22).
Similar data have come from Australia and Europe, with reported odds ratios for IVF versus natural conception of 3–4. I tell patients, therefore, that it's not just one place or one study suggesting risk. Indeed, it's a meaningful risk factor.
▸ Monochorionic twins. In a systemic literature review we conducted several years ago that included 40 fetuses with CHDs among 830 fetuses from monochorionic/diamniotic twin gestations, the rate of CHDs in these twin gestations was significantly higher than the prevalence rate of CHDs in the general population (J. Ultrasound Med. 2007;26:1491-8).