Prolonged QT Interval and SIDS
ABSTRACT & COMMENTARY
Synopsis: Neonatal EKGs were performed in a prospective study in more than 34,000 newborns. Twenty-four of these infants died of presumed sudden infant death syndrome (SIDS). Ten of these 24 infants had prolonged QTc intervals (QT intervals corrected for heart rate). Schwartz and associates suggest that a prolonged QTc is associated with an increased incidence of SIDS.
Source: Schwartz PJ, et al. Prolongation of the QT interval and the sudden infant death syndrome. N Engl J Med 1998;338(24):1709-1714.
Schwartz and associates report findings from an extremely ambitious prospective study that spanned 19 years. They recorded a standard EKG in 34,442 3- to 4-day-old infants and then performed telephone follow-up at one year to determine the incidence of death due to SIDS or other causes. Incidentally, the diagnosis of SIDS was based on an adequate negative postmortem examination. Follow-up data were obtained on an amazing 96% of enrolled infants, and distributions for various conduction intervals were calculated.
The QT interval can be corrected for heart rate (QTc) by dividing the measured QT interval by the square root of the preceding R-R interval (Bazett’s formula). In this study population, the mean QTc interval for all newborns was 400 ± 20 msec and did not differ between the genders. The 97.5th percentile was 440 msec, and infants with a QTc longer than this were considered to have a prolonged QTc.
In the first year of life, there were 34 deaths (24 from presumed SIDS and 10 from other causes). Twelve of the 24 infants who died from SIDS had a QTc greater than 440 msec, while all 10 who died from other causes had a QTc less than 440 msec. In fact, Schwartz et al report that a multiple logistic regression and analysis revealed that only a prolonged QTc was a significant predictor of SIDS, with an absolute risk of 1.53% and an odds ratio of 41.3 with a confidence interval of 95%.
Comment by Alan Friedman, MD, FAAP
Prolongation of the QT interval favors the occurrence of lethal arrhythmias and is associated with an increased risk of sudden death in several clinical, inherited conditions such as the Romano-Ward Syndrome, the Jervell, Lange-Nielsen Syndrome, and even in apparently normal, healthy persons. The typical arrhythmia associated with a prolonged QT interval is a ventricular tachycardia, often referred to as "torsade de pointes," because the wide ventricular complexes in this arrhythmia resemble the shape of a ribbon that has been twisted on its long axis.
This study presents evidence of an association between SIDs and a long QTc interval, although the nature of the association remains unclear. In addition, several important, but difficult to answer, clinical questions are raised. For instance, is there a potential value in performing a routine EKG in all newborns at 3-4 days? If so, who will read them—pediatricians? pediatric cardiologists? Who will pay for them? While the cost of a single EKG is low compared to many other medical tests, the financial burden for screening every newborn would be substantial.
Before these questions are answered, however, one must pose a more important question: is the EKG a good screening test for identifying infants at risk for SIDS? I believe the data presented suggest that it is not. One must remember that by definition, 2.5% of the enrolled infants had a QTc greater than 440 msec, which equates to 861 infants. Twelve of them died of SIDS, yielding a positive predictive value of 1.4%, a poor yield for any screening test. We must also consider the serious social and emotional effect upon the 98% of families who will be identified as "false-positives" based upon their newborn’s EKG.
When one examines the data presented in the report, only four SIDS infants had QTc intervals greater than 460 msec (3 SD), and only two infants had QTc intervals greater than 500 msec, an interval that all would agree is truly prolonged. Perhaps, then, the area of focus should be narrowed to the profoundly prolonged QTc. It would be interesting to know how many infants enrolled, alive and dead, had QTc intervals greater than 500 msec, as these children are likely to have a long QT syndrome (LQTS), rather than a prolonged QT interval. The clinical ramifications of the former are clear, while those of the latter are not. It would also be interesting to have these infants undergo genetic testing to determine if they carry any of the identified abnormalities of cellular channels associated with LQTS. In addition, family history of arrhythmia, sudden death, and EKG findings of parents and siblings would be useful to further the diagnosis.
With regard to the implication that prolonged QTc is a major cause of SIDS, one must remember that numerous infants with so-called "near-miss SIDS" have been observed in hospitalized infants on monitors without a single report of "torsade de pointes" or other significant ectopy. Furthermore, Schwartz et al present no evidence to document that the study infants with prolonged QTC and SIDS had any ventricular ectopy, arrhythmia, or tachycardia.
In summary, this interesting study has raised questions about SIDS, a perplexing and devastating problem. It appears as if there may be an association, direct or indirect, between a prolonged QTc interval and SIDS in some infants who died from presumed SIDS. However, we do not yet know that arrhythmia was the mechanism for SIDS in these infants. Before we change our management practice, it is imperative that we better define the nature of a prolonged QTc interval in infancy, its association (if any) to LQTS, and its possible importance in SIDS. Physicians must resist the temptation to advocate for widespread EKG monitoring of all newborns until there is evidence that this would be a useful, practical, and responsible use of resources and diagnostic strategy.
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