Littman
Vol. 6, No. 3, 1975
|
Neuropadiatrie
PERIPHERAL NERVE MATURATION IN PREMATURE INFANTS B. Littman
Littman, B.: Peripheral nerve maturation in premature infants. Neuropadiatrie 6: 284—291 (1975). The association of peripheral nerve conduction velocity and conceptional age in premature infants is well established. However, the impact of premature birth on the rate of maturation of peripheral nerves is unclear. In this study a group of 119 premature infants and 32 term infants had nerve conduction velocity determinations. The correlation of velocity and conceptional age is significant. There appears to be no effect upon nerve conduction velocity by the occurrence of prenatal or postnatal events. It is unclear whether extrauterine rates of increase of velocity in prematures are comparable to intrauterine rates, but testing of prematures after they have reached their expected date of birth shows them to have identical mean values to term infants tested at term. Peripheral nerve maturation
nerve conduction velocity
Introduction The development of peripheral nerve myelination is known to begin in early gestation, its initial appearance being about 12 weeks postmenstrual age (Gamble 1966). This process continues to mature throughout gestation. It is possible to demonstrate the presence of myelin through direct anatomic study and by the indirect method of nerve conduction velocity (Dunn, J. S. 1970, Dunn, H. G. 1964). As with myelination, peripheral nerve conduction velocity (NCV) shows increasing rates of development through pregnancy and infancy reaching adult levels at 3-4 years of age (Cerra 1962,
Received: June 2, 1975
prematurity
perinatal events
Schulte 1968, Thomas 1960, Baer 1965, Wagner 1972, Gamstorp 1963). The value of this technique in assessing myelination and gestational age has been shown with certain limitations (Dubowitz 1968, Moosa 1972, Blom 1971). It has also been the impression of many that this process matures independently of events outside of the peripheral nervous system; these events include metabolic disorders, anoxic episodes, inappropriate size for gestational age, hyperbilirubinemia and certain signs suggestive of central nervous system dysfunction such as "hyperexcitability and apathy" (Schulte 1968, Blom 1971). Also certain maternal disorders
Accepted: July 8, 1975
Address: B. L., Department of Pediatrics, Devision of Child Development, School of Medicine, University of California, Los Angeles, California 90024 Acknowledgement: Research Supported in part by NICHD Contract No. l-HD-3-2776 and NICHD Grant No. HD-4612, Mental Retardation Research Center, UCLA. Computing assistance was obtained from the Health Sciences Computing Facility, UCLA, supported by N I H Special Resources, Grant No. RR-3.
284
Downloaded by: Universite de Sherbrooke. Copyrighted material.
Department of Pediatrics, School of Medicine, University of California at Los Angeles, Los Angeles, California
Peripheral nerve maturation in premature infants
There is disagreement, however, over the impact of premature birth itself on the rate of increase of myelination and therefore on the NCV. Blom and Finnstrom find that ". . . the process of maturation of peripheral nerves (as judged by the NCV) continues at an unchanged speed after delivery. . ." (Blom 1971). Thus prematures tested at their expected date of birth by them did not differ from term infants tested at their expected date of birth. However, Moosa and Dubowitz found contradictory evidence supporting their hypotheses that "For the first few weeks after birth the peripheral nerves of the preterm infant thus seem to mature at a slightly slower rate than over the same period in utero (Moosa 1971). There is evidence that other neurologic processes in infants mature in an extra-uterine environment similar to those in infants remaining intrauterine such that measuring them in prematures at their expected date of birth reveals no differences from term infants. These include sleep organization, electroencephalography, various neurologic responses and sensory evoked potentials (Parmelee 1967, Parmelee 1968, Finnstrom 1971, Robinson 1966, Howard in prep., Hrbek 1973). Others, however, have disagreed, presenting evidence that premature infants at term are neurologically different in some respects from their term counter-
parts (Watanabe 1973, Saint-Anne Dargassies 1966). Work was undertaken to explore the following: (1) to reconfirm the association of peripheral NCV and conceptional age. (2) to assess the effects of prenatal and postnatal events on the development of NCV using two quantitative measures we have standardized and (3) to explore the impact of an extra-uterine existence on the NCV and therefore on the process of myelination in premature infants. Methods of study Nerve Conduction Velocity (NCV) determinations were done on all infants using the right ulnar nerve. The TECA-4 EMG System was employed with surface electrodes for stimulating and recording. Square wave pulses of 0.2-1 millisecond duration of supramaximal voltages were administered in the manner of Hodes et al. (Hodes 1948). All responses were photographed concurrent with a time scale divided into tenths of a millisecond and surface distances between elbow and wrist were measured to the nearest millimeter. Velocity was calculated by subtracting the muscle response latencies of wrist from elbow and dividing that into the distance between the two points of stimulation. Rectal temperatures were stable for all measurements and remained between 36.8 degrees and 37.5 degrees centigrade. Infants requiring temperature assistance were examined with the aid of overhead radiant heating.
Downloaded by: Universite de Sherbrooke. Copyrighted material.
appear to have no effect on NCV, e. g., toxemia and diabetes (Schulte 1971, Schulte 1969).
Vol. 6, No. 3, 1975
For prenatal and postnatal events assessment two instruments developed by us labelled Obsteric Complications Scale (OCS) and Postnatal Factors (PNF) were employed1 ( L i t t m a n in prep.) The OCS scores 41 events in the maternal medical history and includes any past medical difficulties, problems during pregnancy such as infection or metabolic disorders and any events of medical significance during labor and delivery. The P N F scores 10 events occurring during the first month of life of the infant including infections, respiratory distress, metabolic abnormalities (including electrolytes), convulsions and other medical factors. Mean scores for the OCS and P N F were derived from a random population comprised of full term newborns, prematures and sick term infants. In the following, gestational age is defined as age in days from the onset of the maternal last menstrual period to birth. Conceptional age is age in days from onset of maternal last menstrual period to the day of examination. Gestational and conceptional age determinations were made on the basis of maternal last menstrual period only. One hundred and nineteen premature infants (gestational age less than 259 days and birth weight less than 2500 grams) and 32 terms infants (gestational age 266 to 295 days and birth weight greater than 2500 grams) were enlisted for the study (Table I). All infants where there was confusion
' Available
o n request t o the author
Table I
1
Neuropidiatrie
Conceptional age of populauion at N C V determinaoion Number of determinations a t that age
Conceptional age (days)
Prematures (n = 119) 5 5
9 11
2 27 56 4
Terms (n = 32) 32
Table 11 Repeated N C V determinations
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Littman
and y = conceptional age in days. The 95 % confidence limits for estimating conceptional age from NCV are f 28.95 days. There were no sex differences. If the correlation is limited to only those infants measured within two weeks of delivery, (32 terms, 23 prematures) the coefficient is greater (r = 0.66, p < 0.01). However, this latter group represents the same number of term infants but fewer prematures then the first. The increased correlation with conceptional age in this subgroup may reflect the fact that there is more potential for error in prematures, primarily in measurement of nerve length. With fewer prematures in the group this cause of variability is reduced.
zbout maternal last menstrual period had been previously excluded. Eighty eight of the above premature infants had at least one determination at term. A further 21 had 2 serial examinations at varying periods after their birth (Table 11). Only one of these two latter serial determinations was used in the following calculations except where specified otherwise.
Results NCV and conceptional age
Significant correlation was found between NCV and conceptional age (r = 0.475, p < 0.01). This is shown in Figure 1. The regression formula for these data is y = 228.15 + 1.83 x, where x = NCV in meters per second
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Downloaded by: Universite de Sherbrooke. Copyrighted material.
Peripheral nerve maturation in premature infants
Littman
Vol. 6, No. 3, 1971
200
1
I
Intrauterine and extrauterine NCV development Using the regression formula generated from the data on the 151 NCV determinations, a slope for the expected rate of increase of NCV through gestation was produced. For the 21 prematures who had two examinations the slopes of the rate of increase of their NCV was obtained and compared to that which would be predicted from the data above (Figure 2). Significant difference was found between the obtained slope of the serially tested group and the predicted slope, with the rate of increase of the NCV of the twice examined infants less then would be expected. A t test for obtained against predicted rates confirmed this difference (t = 3.55, p 0.01). I t is interesting
I
Vol. 6, No. 3, 1975
|
Neuropadiatrie
PERIPHERAL NERVE MATURATION IN PREMATURE INFANTS B. Littman
Littman, B.: Peripheral nerve maturation in premature infants. Neuropadiatrie 6: 284—291 (1975). The association of peripheral nerve conduction velocity and conceptional age in premature infants is well established. However, the impact of premature birth on the rate of maturation of peripheral nerves is unclear. In this study a group of 119 premature infants and 32 term infants had nerve conduction velocity determinations. The correlation of velocity and conceptional age is significant. There appears to be no effect upon nerve conduction velocity by the occurrence of prenatal or postnatal events. It is unclear whether extrauterine rates of increase of velocity in prematures are comparable to intrauterine rates, but testing of prematures after they have reached their expected date of birth shows them to have identical mean values to term infants tested at term. Peripheral nerve maturation
nerve conduction velocity
Introduction The development of peripheral nerve myelination is known to begin in early gestation, its initial appearance being about 12 weeks postmenstrual age (Gamble 1966). This process continues to mature throughout gestation. It is possible to demonstrate the presence of myelin through direct anatomic study and by the indirect method of nerve conduction velocity (Dunn, J. S. 1970, Dunn, H. G. 1964). As with myelination, peripheral nerve conduction velocity (NCV) shows increasing rates of development through pregnancy and infancy reaching adult levels at 3-4 years of age (Cerra 1962,
Received: June 2, 1975
prematurity
perinatal events
Schulte 1968, Thomas 1960, Baer 1965, Wagner 1972, Gamstorp 1963). The value of this technique in assessing myelination and gestational age has been shown with certain limitations (Dubowitz 1968, Moosa 1972, Blom 1971). It has also been the impression of many that this process matures independently of events outside of the peripheral nervous system; these events include metabolic disorders, anoxic episodes, inappropriate size for gestational age, hyperbilirubinemia and certain signs suggestive of central nervous system dysfunction such as "hyperexcitability and apathy" (Schulte 1968, Blom 1971). Also certain maternal disorders
Accepted: July 8, 1975
Address: B. L., Department of Pediatrics, Devision of Child Development, School of Medicine, University of California, Los Angeles, California 90024 Acknowledgement: Research Supported in part by NICHD Contract No. l-HD-3-2776 and NICHD Grant No. HD-4612, Mental Retardation Research Center, UCLA. Computing assistance was obtained from the Health Sciences Computing Facility, UCLA, supported by N I H Special Resources, Grant No. RR-3.
284
Downloaded by: Universite de Sherbrooke. Copyrighted material.
Department of Pediatrics, School of Medicine, University of California at Los Angeles, Los Angeles, California
Peripheral nerve maturation in premature infants
There is disagreement, however, over the impact of premature birth itself on the rate of increase of myelination and therefore on the NCV. Blom and Finnstrom find that ". . . the process of maturation of peripheral nerves (as judged by the NCV) continues at an unchanged speed after delivery. . ." (Blom 1971). Thus prematures tested at their expected date of birth by them did not differ from term infants tested at their expected date of birth. However, Moosa and Dubowitz found contradictory evidence supporting their hypotheses that "For the first few weeks after birth the peripheral nerves of the preterm infant thus seem to mature at a slightly slower rate than over the same period in utero (Moosa 1971). There is evidence that other neurologic processes in infants mature in an extra-uterine environment similar to those in infants remaining intrauterine such that measuring them in prematures at their expected date of birth reveals no differences from term infants. These include sleep organization, electroencephalography, various neurologic responses and sensory evoked potentials (Parmelee 1967, Parmelee 1968, Finnstrom 1971, Robinson 1966, Howard in prep., Hrbek 1973). Others, however, have disagreed, presenting evidence that premature infants at term are neurologically different in some respects from their term counter-
parts (Watanabe 1973, Saint-Anne Dargassies 1966). Work was undertaken to explore the following: (1) to reconfirm the association of peripheral NCV and conceptional age. (2) to assess the effects of prenatal and postnatal events on the development of NCV using two quantitative measures we have standardized and (3) to explore the impact of an extra-uterine existence on the NCV and therefore on the process of myelination in premature infants. Methods of study Nerve Conduction Velocity (NCV) determinations were done on all infants using the right ulnar nerve. The TECA-4 EMG System was employed with surface electrodes for stimulating and recording. Square wave pulses of 0.2-1 millisecond duration of supramaximal voltages were administered in the manner of Hodes et al. (Hodes 1948). All responses were photographed concurrent with a time scale divided into tenths of a millisecond and surface distances between elbow and wrist were measured to the nearest millimeter. Velocity was calculated by subtracting the muscle response latencies of wrist from elbow and dividing that into the distance between the two points of stimulation. Rectal temperatures were stable for all measurements and remained between 36.8 degrees and 37.5 degrees centigrade. Infants requiring temperature assistance were examined with the aid of overhead radiant heating.
Downloaded by: Universite de Sherbrooke. Copyrighted material.
appear to have no effect on NCV, e. g., toxemia and diabetes (Schulte 1971, Schulte 1969).
Vol. 6, No. 3, 1975
For prenatal and postnatal events assessment two instruments developed by us labelled Obsteric Complications Scale (OCS) and Postnatal Factors (PNF) were employed1 ( L i t t m a n in prep.) The OCS scores 41 events in the maternal medical history and includes any past medical difficulties, problems during pregnancy such as infection or metabolic disorders and any events of medical significance during labor and delivery. The P N F scores 10 events occurring during the first month of life of the infant including infections, respiratory distress, metabolic abnormalities (including electrolytes), convulsions and other medical factors. Mean scores for the OCS and P N F were derived from a random population comprised of full term newborns, prematures and sick term infants. In the following, gestational age is defined as age in days from the onset of the maternal last menstrual period to birth. Conceptional age is age in days from onset of maternal last menstrual period to the day of examination. Gestational and conceptional age determinations were made on the basis of maternal last menstrual period only. One hundred and nineteen premature infants (gestational age less than 259 days and birth weight less than 2500 grams) and 32 terms infants (gestational age 266 to 295 days and birth weight greater than 2500 grams) were enlisted for the study (Table I). All infants where there was confusion
' Available
o n request t o the author
Table I
1
Neuropidiatrie
Conceptional age of populauion at N C V determinaoion Number of determinations a t that age
Conceptional age (days)
Prematures (n = 119) 5 5
9 11
2 27 56 4
Terms (n = 32) 32
Table 11 Repeated N C V determinations
Downloaded by: Universite de Sherbrooke. Copyrighted material.
Littman
and y = conceptional age in days. The 95 % confidence limits for estimating conceptional age from NCV are f 28.95 days. There were no sex differences. If the correlation is limited to only those infants measured within two weeks of delivery, (32 terms, 23 prematures) the coefficient is greater (r = 0.66, p < 0.01). However, this latter group represents the same number of term infants but fewer prematures then the first. The increased correlation with conceptional age in this subgroup may reflect the fact that there is more potential for error in prematures, primarily in measurement of nerve length. With fewer prematures in the group this cause of variability is reduced.
zbout maternal last menstrual period had been previously excluded. Eighty eight of the above premature infants had at least one determination at term. A further 21 had 2 serial examinations at varying periods after their birth (Table 11). Only one of these two latter serial determinations was used in the following calculations except where specified otherwise.
Results NCV and conceptional age
Significant correlation was found between NCV and conceptional age (r = 0.475, p < 0.01). This is shown in Figure 1. The regression formula for these data is y = 228.15 + 1.83 x, where x = NCV in meters per second
- .$r; 1
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0
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.
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10 15 20 25 30 35 40 ULNAR NERVE CONDUCTION VELOCITY (meterskec) Fig. 1
Downloaded by: Universite de Sherbrooke. Copyrighted material.
Peripheral nerve maturation in premature infants
Littman
Vol. 6, No. 3, 1971
200
1
I
Intrauterine and extrauterine NCV development Using the regression formula generated from the data on the 151 NCV determinations, a slope for the expected rate of increase of NCV through gestation was produced. For the 21 prematures who had two examinations the slopes of the rate of increase of their NCV was obtained and compared to that which would be predicted from the data above (Figure 2). Significant difference was found between the obtained slope of the serially tested group and the predicted slope, with the rate of increase of the NCV of the twice examined infants less then would be expected. A t test for obtained against predicted rates confirmed this difference (t = 3.55, p 0.01). I t is interesting
I
