Autonomic alterations in cocaine-exposed infants.

BACKGROUND: Heart rate variability (HRV) reflects autonomic control of the heart. After intrauterine cocaine exposure, asymptomatic newborn infants within 72 hours of life have decreased HRV. It is unknown whether these alterations are transient (acute effect) or persist in older infants and possibly reflect a teratogenic effect of cocaine. METHODS: This study prospectively evaluated HRV in 2- to 6-month-old infants who were exposed to cocaine in-utero (Group 1, n = 71). Their data were compared to normal controls (Group 3, n = 77) and to newborns exposed to drugs other than cocaine (Group 2, n = 89). Based on our previous study, heavy and light cocaine exposure was also defined a priori as the amount of cocaine used during the pregnancy that was more than or less than the 70th percentile, respectively. RESULTS: At the age of 2 to 6 months, infants with in-utero cocaine exposure had higher vagal tone and higher HRV (total power) than normal controls (no exposure to drugs). Most of this increase in vagal tone occurred in the light-cocaine-exposure group. HRV and vagal tone in the heavy-cocaine-exposure group were similar to the noncocaine-exposed group. CONCLUSIONS: At 2 to 6 months of age, asymptomatic infants exposed to cocaine in-utero have recovered from lower HRV seen within 72 hours of age. Infants exposed to light cocaine recovered by a rebound by increasing their vagal tone to above-normal levels. A similar response was blunted in heavily-cocaine-exposed infants. These alterations noted at follow up suggest a possible teratogenic effect of cocaine on the developing autonomic system.

Diastolic alterations in infants exposed to intrauterine cocaine: a follow-up study by color kinesis.

BACKGROUND: During the first 48 hours of life, newborn infants exposed to cocaine in utero have left ventricular diastolic segmental abnormalities. It is unknown whether these abnormalities are transient because of short-term effects or persist in older infants, possibly reflecting a teratogenic effect of cocaine. METHODS: This study prospectively evaluated global and segmental systolic and diastolic cardiac parameters by color kinesis. The patients were 2- to 6-month-old infants who were exposed to cocaine in utero (N = 56). Their data were compared with normal control patients with no intrauterine drug exposure (N = 60) and newborns exposed to drugs other than cocaine (N = 72). RESULTS: At the age of 2 to 6 months, there was no significant difference in the measured color kinesis parameters among the cocaine-exposed and the 2 control groups (infants prenatally exposed to other drugs and no drugs). Infants exposed to heavy cocaine prenatally, as compared with the noncocaine-exposed group, had a significant (P =.007) increase in septal fractional area change during left ventricular filling. CONCLUSIONS: At 2 to 6 months of age, infants have recovered from initial left ventricular diastolic segmental alterations seen in the first 48 hours of life except for the septal wall in the heavily cocaine-exposed group.

Heart rate variability by triangular index in infants exposed prenatally to cocaine.

BACKGROUND: In adults, heart rate variability triangular index (HRVi) is a highly reproducible measure of heart rate variability (HRV), which makes it more suitable for use in longitudinal studies. Although normative data have been published for newborns, studies in infants with pathological conditions are lacking. METHODS: From 1997 to 2000, within the first 4 days of life, we prospectively evaluated HRVi in cocaine-exposed asymptomatic newborns (N = 97) by Holter monitoring. Their data were compared with infants from two control groups (one with no in utero drug exposure, N = 102; the other with exposure to alcohol, nicotine, or marijuana but no cocaine, N = 111). RESULTS: In assessing concordance between and within operators for HRVi, the intraclass correlations were 0.983 (95% CI: 0.958, 0.994) and 0.997 (95% CI: 0.984, 0.999), respectively. Infants with in utero cocaine exposure had significantly (P < 0.0001) lower HRVi than those exposed to other drugs and to no drugs in utero. If abnormal HRVi is defined as < fifth percentile for the no drug exposed group (HRVi < 8), 10% of the cocaine-exposed newborns, in contrast to 2% in each of the control groups (P = 0.003) had abnormal values. CONCLUSION: HRVi is a reliable measure to study heart rate variability in newborns. Asymptomatic infants with in utero cocaine exposure have lower HRVi. Our study supports the clinical use of an abnormal HRVi as a value < 8 for newborn infants.

Diastolic filling abnormalities by color kinesis in newborns exposed to intrauterine cocaine.

Because cocaine crosses the placenta, we prospectively evaluated global and segmental systolic and diastolic cardiac function by color kinesis in clinically asymptomatic newborns who were exposed to cocaine in utero (group 1, n = 82). Their data were compared with normal controls (group 3, n = 87) and newborns exposed to drugs other than cocaine (group 2, n = 108). During left ventricular filling, newborns exposed to cocaine, compared with groups 2 and 3, had significantly (P <.05) higher global fractional area change (%) (76 +/- 10.3 vs 72 +/- 9.4 and 72 +/- 9.1, respectively), regional fractional area changes (%) for the anterior, septal, inferior, and lateral wall, and in the index of asynchrony (at 50% filling 13.2 +/- 5.8 vs 11.3 +/- 4.1 and 11.6 +/- 4.2, respectively). There were no significant differences in systolic function among the 3 groups. Prenatal cocaine exposure in asymptomatic infants leads to higher global and segmental fractional area changes and asynchrony during diastole. The significance and course of these alterations require further investigation.

Heart rate variability in healthy newborn infants.

In adults and older children, heart rate variability (HRV) is frequently used to study autonomic function noninvasively. Normal values of HRV in newborn infants, however, are not widely available. This problem may be partially attributed to the lack of standardization of different methods. This study assessed HRV in normal newborn infants using 24-hour Holter monitoring. From 1997 to 2000, we prospectively evaluated frequency- (spectral analysis), geometric-, and time-domain indexes of HRV in normal term infants. Ninety-six asymptomatic infants who were <72 hours old were studied. Frequency-domain parameters (power in the high, low, very low, ultra low, and total frequency domains), a geometric parameter (HRV triangular index), and time-domain parameters (SDNN, SDANN, SDNNi, r-MSSD, s-NN50) are reported as means +/- SD, medians, and 5th and 95th percentiles to establish the normative values for newborns. A high degree of correlation (r > or = 0.85, p <0.0001) was noted among the 3 vagal tone dependent parameters, such as high-frequency power (frequency domain), r-MSSD, and s-NN50 (time domain). Our study supports the use of vagal dependent time-domain parameters like r-MSSD and sNN50 as surrogates for high-frequency power in newborns. Because the data are reported as means +/- SD, medians, and 5th and 95th percentiles, their use facilitates the study of parasympathetic and sympathetic activity in comparable populations.