Prolongation of the QT interval and the sudden infant death syndrome.

BACKGROUND: The sudden infant death syndrome (SIDS) is multifactorial in origin, but its causes remain unknown. We previously proposed that prolongation of the QT interval on the electrocardiogram, possibly resulting from a developmental abnormality in cardiac sympathetic innervation, may increase the risk of life-threatening ventricular arrhythmias and contribute to this devastating disorder. We prospectively tested this hypothesis. METHODS: Between 1976 and 1994, we recorded electrocardiograms on the third or fourth day of life in 34,442 newborns and followed them prospectively for one year. The QT interval was analyzed with and without correction for the heart rate. RESULTS: One-year follow-up data were available for 33,034 of the infants. There were 34 deaths, of which 24 were due to SIDS. The infants who died of SIDS had a longer corrected QT interval (QTc) than did the survivors (mean [+/-SD], 435+/-45 vs. 400+/-20 msec, P<0.01) and the infants who died from causes other than SIDS (393+/-24 msec, P<0.05). Moreover, 12 of the 24 SIDS victims but none of the other infants had a prolonged QTc (defined as a QTc greater than 440 msec). When the absolute QT interval was determined for similar cardiac-cycle lengths, it was found that 12 of the 24 infants who died of SIDS had a QT value exceeding the 97.5th percentile for the study group as a whole. The odds ratio for SIDS in infants with a prolonged QTc was 41.3 (95 percent confidence interval, 17.3 to 98.4). CONCLUSIONS: Prolongation of the QT interval in the first week of life is strongly associated with SIDS. Neonatal electrocardiographic screening may permit the early identification of a substantial percentage of infants at risk for SIDS, and the institution of preventive measures may therefore be possible.

Burst suppression and impairment of neocortical ontogenesis: electroclinical and neuropathologic findings in two infants with early myoclonic encephalopathy.

We report the electroclinical and neuropathologic correlations in 2 children aged 2.5 months affected by early myoclonic encephalopathy characterized by epileptic seizures, erratic myoclonus, and an EEG pattern of burst suppression. Despite different etiologies, the neuropathologic findings showed similar abnormalities in both cases, with no substantial impairment of the myelination processes. Islands of matrix tissue scattered in the periventricular region and neurons aligned marginally in the bulbar olives were detected. The presence of numerous large spiny neurons dispersed in the white matter along the axons of the cortical gyri was the most striking finding. The neurons have been interpreted as abnormally persisting interstitial cells in 2.5-month-old children. These early generated neurons, normally present during neocortical histogenesis, are programmed to die near the end of gestation or soon after birth. The interstitial cells are regarded as a waiting compartment of afferent fibers during cortical development. Their persistence in our patients represents an anatomic condition for cortical disconnection providing a pathophysiologic basis to burst-suppression phenomena.

The QT interval throughout the first 6 months of life: a prospective study.

A prospective electrocardiographic study was designed to establish baseline values for electrocardiographic measurements, with specific reference to the QT interval during infancy, and to test the "QT hypothesis" for the sudden infant death syndrome (SIDS). In this ongoing study, ECGs are recorded on the fourth day of life and in the second, fourth and sixth months. The state of health at 1 year is ascertained by a phone call. So far, 4205 newborns have been enrolled. The mean QTc (QT interval corrected for heart rate) was 397 +/- 18 msec (+/- SD) at the fourth day, 409 +/- 15 msec (p less than 0.0001) at the second month, and 406 +/- 15 msec at the fourth month; by the sixth month, it returned to 400 +/- 14 msec. In 88 newborns, the QTc increased by over 40 msec at the second month. Among the 2000 infants checked at 1 year, there have been three sudden and unexpected deaths. The QTc of one of the victims at the fourth day was 563 msec, which exceeded the mean by more than 9 standard deviations, while the QTc of the other SIDS victims exceeded the mean by more than 2 and 3 standard deviations. These results are consistent with the "QT hypothesis," but more data are necessary before any conclusion on the potential relationship between QT interval prolongation and SIDS can be drawn. This study provides definitive waking normal values for QT interval in infancy and indicates that the QT interval lengthens physiologically and temporarily during the first months of life. In some infants, this lengthening may transiently impair cardiac electrical stability.

Primary proximal renal tubular acidosis; A therapeutical approach and long term follow-up.

This paper reports a case of proximal renal tubular acidosis followed during 4 years, in a 4-year-old girl. High doses of alkali could not be administered owing to gastric intolerance of the patient; diuretic therapy carries the risk of causing severe dehydration or hypotension. We administered such a dose of NaHCO3 to obtain a normal blood pH--with persistent hyperventilation-, subnormal bicarbonatemia, and acid urine. This treatment could cause an improvement of rickets, growth and laboratory data. At present, the biochemical data, including urinary excretion of bicarbonate with normal bicarbonatemia, are normal; this indicates a spontaneous recovery of the syndrome. We think that low doses of alkali are useful in the transient form of proximal renal tubular acidosis to prevent bone lesions and failure to thrive. But even in the irreversible form of this syndrome--when high alkali doses and diuretics cause dangerous effects--this therapy may be useful to treat some symptoms.