Incidence of Neonatal Seizures in Harris County, Texas,

Transcription

1 American Journal Epidemiology Copyright C 1999 by The Johns Hopkins Universtty School Hygiene and Public Health All rights reserved Vol.15, 7 Printed in USA. Incidence Neonatal Seizures in Harris County, Texas, Rima M. Saliba, 1 J. Fred Annegers, 1 D. Kim Waller, 1 Jon E. Tyson, 1 ' 2 and Eli M. Mizrahi 3 " 5 This study estimated the incidence clinical neonatal seizures among infants born between 1992 and 1994 in Harris County, Texas, a county with a large and ethnically diverse population. Infants with neonatal seizures were ascertained from four sources: hospital discharge diagnoses, birth certificates, death certificates, and a study neonatal seizures conducted concurrently with this study at a large tertiary care center in Houston, Texas. There were 27 cases clinical neonatal seizures among 116,48 live births (an incidence per 1, live births). The incidence was highest among infants weighing less than 1,5 g (19/1,) and decreased as birth weight increased. There was no significant difference in incidence by ethnicity. Twenty-six percent the seizures (54/27) occurred after the infants had been discharged from the hospital where they were born. The incidence neonatal seizures in Harris County was lower than the incidence reported recently for Fayette County, Kentucky, for (3.5/1,) and for Newfoundland, Canada, for (2.5/1,), but was higher than the incidence estimated for Rochester, Minnesota, for (1/1,). Am J Epidemiol 1999; 15: convulsions; incidence; infant, very low birth weight; neonatal diseases and abnormalities; seizures Seizures in newborns are associated with a 2 percent risk mortality and an increased risk neurodevelopmental impairment, including cerebral palsy, mental retardation, and epilepsy (1). The reported frequency neonatal seizures has varied between 1 and 14 per 1, live births (2-11). Most these estimates were based on referral series (2-8) and preceded technologic advancements in neonatal care, which are expected to have modified the incidence neonatal seizures (9). Current information on the incidence neonatal seizures within defined populations is limited to two reports. Ronen and Penny (1) reported an incidence 2.5 per 1, live births in Newfoundland, Canada, for ; and Lanska et al. (11) reported an incidence 3.5 per 1, live births in Fayette County, Kentucky, for In Rochester, Minnesota, Hauser estimated an incidence 1 per 1, Received for publication August 11, 1998, and accepted for publication March 1, Abbreviations: Cl, confidence interval; ICD-9-CM, International Classification Diseases, Ninth Revision, Clinical Modification. 1 University Texas School Public Health, Houston, TX. 2 Department Pediatrics, University Texas School Medicine, Houston, TX. 3 Section Neurophysiology, Department Neurology, and Section Pediatric Neurology, Department Pediatrics, Baylor College Medicine, Houston, TX. 4 The Methodist Hospital, Houston, TX. 'Texas Children's Hospital, Houston, TX. Reprint requests to Dr. J. Fred Annegers, University Texas School Public Health, 12 Herman Pressler, Houston, TX 773. live births for the period (A. Hauser, Mayo Clinic, personal communication, 1996). In this study, we estimated the incidence recognized clinical neonatal seizures occurring between 1992 and 1994 in Harris County, Texas, a county with a large and ethnically diverse population. MATERIALS AND METHODS The objective the study was to ascertain cases neonatal seizure in infants born to residents Harris County between September 1, 1992, and August 31, Neonatal seizures were ascertained from four sources (table 1, figure 1): discharge diagnoses at birth hospitals and neonatal intensive care units; birth certificates; death certificates; and a concurrent prospective study neonatal seizures conducted at Texas Children's Hospital, a large tertiary care center in Houston, Texas. The primary source case ascertainment was discharge diagnoses obtained from birthing hospitals serving residents Harris County. All but one the 44 delivery hospitals in the area agreed to participate in the study. The exception was a community hospital in an adjacent county, where only.2 percent the births occurred. Requests were made to all participating hospitals for a list infants born during the study period and diagnosed in the first 5 months life with an International Classification Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) (12) code 763

2 764 Saliba et al. TABLE 1. Sources ascertainment Infants diagnosed with neonatal seizures, Harris County, Texas, Source eligible infants nonellglble infants Nonresktency Other reason Total no. Infants Hospital discharge diagnoses Vital statistics Clinical study* Total A concurrent clinical study neonatal seizures conducted at Texas Children's Hospital, Houston, Texas. 345 (seizure/epilepsy), 78.3 (convulsion), or 79. (convulsion in newborn). Of the 43 participating hospitals, nine (three private/university hospitals, two public/university hospitals, and four private community hospitals) had a level in nursery. Levels I, n, and in were defined according to the criteria the American Academy Pediatrics' Guidelines for Perinatal Care (13). In 1989, a code for neonatal seizures was added to the supplemental section the Texas birth certificate. The Texas Department Health provided the birth certificates 26 Harris County newborns who had been coded as having neonatal seizures. The Texas Department Health also provided three death certificates with one the ICD-9-CM codes listed above. Cases were also ascertained from a concurrent study infants with clinical or electrical seizures identified during electroencephalogram-video monitoring, typically lasting no longer than 2 hours, at Texas Children's Hospital. The medical records potential cases (those identified by the above four sources) from hospitals birth, neonatal intensive care units, and other hospital or Discharge diagnoses emergency room visits made during the first 5 months life were reviewed. Information on demographic and clinical variables, including a verbatim transcription the clinical description seizures, was abstracted by one the authors (R. M. S.). Gestational age was estimated based on the date the last menstrual period. Preterm birth was defined as any birth occurring before 37 completed weeks gestation. Very low birth weight was defined as a birth weight less than 1,5 g. Residency the mother in Harris County was verified using information from medical records and local telephone directories. Inclusion criteria were as follows: 1) description a clinical seizure consistent with the definitions proposed by Volpe (1) and Mizrahi and Kellaway (14) and 2) seizures occurring within the first 28 days life for full term infants and within 44 completed weeks conception for preterm infants. The extension to 44 weeks for preterm infants was done in order to include seizures occurring at equivalent conceptual ages for preterm and full term infants. Infants were excluded from the study if 1) the documented seizure was an electrographic seizure recorded during an electroencephalogram without any associated clinical signs, 2) the documented clinical seizure was observed only during electroencephalogram-video monitoring performed for reasons other than suspected seizures, 3) the abnormal movements could be stopped by holding or restraining the limbs the infant, or 4) the clinical seizure was characterized as an apneic episode or the description was limited to nonspecific terms such as "jitteriness," "shaking," or "seizure-like activity." The rationale behind the first two exclusions was ensuring consistency in the methods used to detect seizures, since electroencephalography or electroencephalogramvideo monitoring is not a standard procedure. Incidence according to newborn characteristics was calculated by dividing the number infants with incident seizures by the total number live births. Denominators the incidence were determined from computerized birth certificate data files for the study population. Relative risk estimates and 95 percent confidence intervals (15) were calculated by univariate analysis using Stata 5. (16). Vital statistics Concurrent clinical study (TOP) FIGURE 1. Sources case ascertainment infants diagnosed with neonatal seizures, Harris County, Texas, *TCH, Texas Children's Hospital. RESULTS Ascertainment A total 116,48 infants were born between September 1, 1992, and August 31, 1994, to mothers who resided in Harris County. Among these infants, 44 potential cases neonatal seizure were identified from the following sources: 342 through discharge diagnoses at local hospitals, 29 through vital statistics Am J Epidemiol Vol. 15, 7, 1999

3 Incidence Neonatal Seizures in Harris County, Texas 765 (26 from birth certificates and three from death certificates), and 69 through the concurrent study neonatal seizures at Texas Children's Hospital (table 1). Of the 44 potential cases, only 27 met our inclusion criteria. Exclusions were as follows. Of the 342 infants identified through discharge diagnoses, 14 were excluded because: 1) the mother was not a resident Harris County (n = 96); 2) there was no description seizures in the medical record (n = 4); 3) the seizure occurred after the neonatal period (n = 13); 4) the seizure was electrical only (n = 4); 5) the documented clinical seizure was observed only during electroencephalographic monitoring (n = 1); or 6) the description the seizure did not meet the study criteria (n = 21). This group included five infants in whom abnormal movements could be stopped by holding the limbs and 16 infants for whom the description seizures was limited to "jitteriness" (n = 5), "jerking" (n = 2), "shaking" (n = 2), "apnea" (n = 1), "cyanotic spell" (n = 1), "choking episode" (n = 1), "difficulty breathing while taking a bath and blowing bubbles" (n = 1), "oxygen desaturation with arched back and rigid muscle tone" (n = 1), "quivering abdomen musculature" (n - 1), and "seizure-like activity" (n - 1). In addition, one infant was excluded because the medical record could not be located. This left 22 cases that were ascertained through discharge diagnoses. Of the 29 infants identified through vital statistics, 14 were not eligible for this study, including 13 falsepositive cases and one infant for whom the documented seizure was electrical only. Among the remaining 15 eligible cases, 14 had been ascertained independently through the discharge diagnoses at the local hospitals. One these 14 infants was later excluded because the description the seizure did not meet our study inclusion criteria. Thus, only one additional case was ascertained through vital statistics. Concurrent with this study, 69 infants were enrolled in a prospective clinical study neonatal seizures conducted at Texas Children's Hospital. Of these, 27 infants were not eligible for our study, including 24 infants who were born to non-harris County residents, two who had electrical seizures only, and one infant for whom the documented clinical seizure was observed only during electroencephalographic monitoring. Of the remaining 42 infants, 38 had been ascertained through discharge diagnoses at the local hospitals. Thus, four additional cases were ascertained through the clinical study conducted at Texas Children's Hospital (figure 1). For two these four infants, the discharge diagnoses did not include an ICD-9-CM code corresponding to seizures, and their principal diagnosis was respiratory distress syndrome. Am J Epidemiol Vol. 15, 7, 1999 The extent description the clinical seizures in the medical records was comparable across hospitals. Documentation that an electroencephalogram was performed was present for 95 percent (197/27) the infants with clinical seizures. Thirty-seven percent (72/197) these infants had an electrographic seizure recorded on electroencephalograms. In 25 these infants, the electrographic seizure occurred without simultaneous clinical signs, and in 43 it occurred simultaneously with clinical signs. Four infants had electrographic seizures with or without associated clinical signs. Although these data were noted, electroencephalograms were not used as criteria for case confirmation. The latter was based solely on description the clinical seizure. Incidence by newborn characteristics The overall incidence neonatal seizures was per 1, live births (table 2). It varied slightly by ethnicity, with infants born to Black mothers having a 4 percent increased risk compared with those born to White mothers (relative risk =, 95 percent CI: 1., ). Boys had a 2 percent increased risk over girls, but this was not statistically significant (relative risk =, 95 percent CI:.8, ). Incidence was strongly and inversely related to birth weight (table 2). The risk among infants weighing less than 1,5 g (19./1,) was substantially higher than the risk among those weighing 1,5 g or more (relative risk = 1, 95 percent CI: 8.1, 17.9). The risk decreased to 5./1, for infants weighing 1,5-1,999 g and to 1.3/1, for those weighing 3,5 g or more. A similar gradient increased risk was observed with decreasing gestational age (table 2). This is to be expected, as birth weight and gestational age are strongly correlated. The incidence was 2.4/1, among infants born before 28 completed weeks gestation; it decreased to 7.4/1, for those born between 29 and 32 weeks' gestation and to /1, for full term infants (37^41 weeks). Postterm infants (>42 weeks) had a higher risk (2.6/1,) than full term infants; however, this was only marginally significant statistically. Incidence by hospital birth The incidence neonatal seizures varied according to the hospital birth. Overall, infants born in hospitals with level HI neonatal care were twice as likely to have a diagnosis seizures as those born in hospitals with level II care. There was also variation in the risk seizures within hospitals that had level DI care, especially among infants weighing less than 1,5 g. Very low birth weight infants born in private/univer-

4 766 Saliba et al. TABLE 2. Incidence neonatal County, Texas, seizures according to Infant and maternal characteristics, Harris Variable births cases Risk per 1, live births Relative 95% confidence interval Gender Female* Male 56,794 59, , Ethnicity White* Black Hispanic Other 42,439 24,925 44,611 3, ,.8,.4, 2.2 Birth weight (g) <1,5 1,5-1,999 2,-2,499 2,5-2,999 3,-3,499* 3,5-3,999 24, Length gestation (weeks) * 242 Maternal age (years) < * Parity Primiparous Multiparous* All live births 1 Reference category. 1,473 1,586 5,169 19,199 43,587 32,522 1, ,358 7,86 12,131 3,78 6,858 41,277 31,469 24,47 1,227 1,73 49, 66, ,48 sity hospitals with level HI nurseries were significantly more likely to have a diagnosis seizures (4.7/ 1,) than those born in public/university hospitals (6.5/1,) or private hospitals (6.9/1,) with level HI nurseries (table 3). Incidence by day life The incidence seizure was highest during the first 2 days life and decreased gradually thereafter (figure 2). Thirty-eight percent the 27 infants had their first recognized seizure during the first 2 days life, half by the third day life, 7 percent within the first week, and 93 percent within the first 28 days. The ' ,2,7.6.7, 2.4,2.5.6, 1.3.6, , , 9.6,2.8.9, 3.7.7, ,2.1.8, 1.9.7,.8, 5.1.9, remaining 7 percent (15/27) were preterm infants who were older than 28 days but were under 44 weeks conceptual age at the time the initial seizure was diagnosed. If this last group infants were excluded, the incidence neonatal seizures would be per 1, live births. During the first 28 days life, the frequency seizures by day life was similar for infants weighing less than 2,5 g and those weighing 2,5 g or more. Among the 34 infants weighing less than 2,5 g, eight (24 percent) had their initial seizure recognized on the first day Life, nine (26 percent) on the second or third day Life, nine (26 percent) within the remaining first week life, and eight (24 percent) between the second week and 28 Am J Epidemiol Vol. 15, 7, 1999

5 Incidence Neonatal Seizures in Harris County, Texas 767 TABLE 3. Incidence neonatal seizures according to birth weight and place birth, Harris County, Texas, Place birth Hospital Level III facility All level III facilities Private/university {n = 3) Public/university (n = 2) Private (n = 4) Level II facility (n = 26) Other facility (n = 8) Home birth All births* births 1, <1,5g cases Risk per 1, live births Birth weight births 59,52 16,247 22,71 2,563 45,368 7, ,5 g cases , , ' Total does not include 1,879 infants with unknown birth weight. days life. The corresponding frequencies among the 158 infants weighing 2,5 g or more were 4 (25 percent), 51 (32 percent), 28 (18 percent), and 39 (25 percent). Of the 15 infants who had their first recognized seizure after day 28, three infants weighed 2,5 g or more. I so Incidence after discharge Risk per 1, live'births AD infants (risk per 1, live births) Twenty-six percent (54/27) the infants had their initial seizure after discharge from the hospital birth. Forty-one percent (22/54) these seizures occurred during the first week life, 24 percent during the second week, and 19 percent during the third week IrwTI i il I i n i Days FIGURE 2. Distribution first seizures by day life, Harris County, Texas, Am J Epidemiol Vol. 15, 7, 1999

6 768 Saliba et al. Of the 54 infants who had seizures after discharge from the hospital birth, 1 had been rehospitalized prior to the time the first recognized seizure occurred, 4 were at home, and four were at the emergency room or a private physician's fice. All infants who were not hospitalized at the time the initial seizure occurred were admitted to a neonatal intensive care unit for at least 24 hours and had an electroencephalogram performed on them. Six the 4 infants who had their first recognized seizure at home had, when hospitalized, an electrographic seizure recorded on the electroencephalogram with associated clinical signs, and four had an electrographic seizure unassociated with clinical signs. Most the 54 infants were full term, with an average birth weight 3,26 g and an average gestational age 38 weeks. The ethnic distribution the 54 cases was similar to that the total study population. DISCUSSION This study represents the largest recent populationbased investigation neonatal seizures. To maximize ascertainment, we used multiple sources to identify infants with seizures, extended the search discharge diagnoses to the first 5 months life, and covered hospitals located in counties adjacent to Harris County. We also ascertained seizures occurring before and after discharge from the hospital birth. The incidence neonatal seizures in Harris County, Texas ( per 1, live births) is lower than the incidence reported for Fayette County, Kentucky (3.5/1,) (11) and the incidence reported for Newfoundland, Canada (2.5/1,) (1), but is higher than the incidence estimated for Rochester, Minnesota (1./1,) (A. Hauser, Mayo Clinic, personal communication, 1996). Some the variation in the incidence neonatal seizures reported across studies can be attributed to variation in the method diagnosis neonatal seizures within and across nurseries (17). Although it is difficult to evaluate, such variation is to be expected because the difficulty recognizing seizures among newboms, the variability expertise in witnessing seizures, the type and duration surveillance newborns, and the coding seizure events under appropriate ICD-9-CM codes (17). In Harris County, 54 percent all births occurred in hospitals with a level HI nursery, where the level surveillance and training in recognizing clinical neonatal seizures may be enhanced in comparison with hospitals with a lower level care. Differences in neonatal care might also contribute to variation in seizure diagnosis across nurseries. Such differences include use agents that might make seizures more difficult to identify (e.g., agents that produce neuromuscular blockade and prophylactic antiepileptic drugs, i.e., phenobarbital), management methods that reduce the incidence seizures, or treatment practices that might increase the survival infants at greatest risk seizures. It is unclear whether differences in neonatal care contributed to the higher risk in Fayette County as compared with Harris County, especially during the first 2 days life and among very low birth weight infants, where the differences in incidence were most pronounced (table 4). Differences in methods ascertainment, case definition (type and timing seizures), and study population are unlikely to have contributed significantly to the difference in incidence between Harris County and the other two areas studied (1, 11). Methods ascertainment were similar in Harris County and Fayette County, Kentucky (11). Cases were ascertained retrospectively in both counties on the basis similar discharge diagnoses. In contrast, Ronen and Penny (1) ascertained cases prospectively after training the clini- TABLE 4. Incidence neonatal seizures In Fayette County, Kentucky ( ) and Harris County, Texas ( ) Wo riot-jo VaJkHJW Gender Female Male Ethnicity White Black Hispanic Other Birth weight (g) <1,5 1,5-2,499 2,5-3,999 4, Hospital birth Private/university Level II Timing seizure Day 1 Day 2 Weeki Week 2 Week 3 All Infants Risk per 1, live births Fayette County Harris County Relative risk* (95% Clt) 1.9(1.3,3.) 1.9(,2.9) 2.2(,3.2) 1.9(1.,3.6) 2.9(, 5.5) (.6,4.9) (1.3,2.6) 1.3(.4,3.9) 1.9(, 3.1) (, 3.4) 4. (2.5, 6.4) 2.4(,4.8) (.6,2.1) 1.3(.5,3.3) 1.9(.5,6.9) (,2.6) * Calculated using the incidence in Harris County as the referent t Cl, confidence interval. Am J Epidemiol Vol. 15, 7, 1999

7 Incidence Neonatal Seizures in Harris County, Texas 769 cal staff in seizure diagnosis. Prospective ascertainment according to predetermined criteria allows for more accurate ascertainment neonatal seizures; however, its feasibility within large populations such as that Harris County is limited. The ethnic distribution differed substantially between Harris and Fayette counties; however, this did not contribute to the difference in incidence between the counties, as the twold higher risk in Fayette County was constant within ethnic groups (table 4). Birth weight distributions were similar in both counties. The twold higher risk in Fayette County was sustained within most the birth weight categories, except in very low birth weight infants, where it was threefold higher. Very low birth weight infants constituted less than percent the total population in both counties, and the increased risk in this group would not contribute substantially to the observed increased risk in Fayette County. It is noteworthy that in both Harris and Fayette counties, the incidence seizures among infants born in private/university hospitals with a level III nursery was three times that among infants born in hospitals with a level II nursery. This suggests similar referral patterns for high risk pregnancies in both counties, which could partly account for the increased risk in private/university hospitals. In conclusion, consistent with previous findings (18-21), our study indicates that birth weight is a strong predictor the risk neonatal seizures. It also suggests that, independently birth weight, the pregnancy complications that lead to a premature birth might affect the risk seizures, as reflected in the higher risk among very low birth weight infants bom in private/university referral centers. Although the risk seizures was highest among premature infants, full term infants constituted the majority cases neonatal seizure in our study population. This warrants evaluation risk factors for seizures among preterm and full term infants separately. ACKNOWLEDGMENTS This study was supported by grant NO1-NS from the National Institute Neurological Disorders and Stroke. The authors thank the medical records staff at the participating hospitals for their valuable cooperation, and Sharon Coan and Tony Lam for their assistance with data management. REFERENCES 1. Volpe JJ. Neonatal seizures. In: Neurology the newborn. 3rd ed. Philadelphia, PA: WB Saunders Company, 1995: Bruce DB. The prognostic significance neonatal convulsions. Arch Dis Child 1954;29: Hopkins U. Seizures in the first week life: a study aetiologic factors. Med J Aust 1972;2: Brown JK, Cockbum F, Forfar JO. Clinical and chemical correlates in convulsions the newborn. Lancet 1972;l: Keen JH, Lee D. Sequelae neonatal convulsions: study 112 infants. Arch Dis Child 1973;48: Dennis J. Neonatal convulsions: aetiology, late neonatal status and long-term outcome. Dev Med Child Neurol 1978;2: Eriksson M, Zetterstrom R. Neonatal convulsions: incidence and causes in the Stockholm area Acta Paediatr Scand 1979; 68: Holden KR, Mellits ED, Freeman JM. Neonatal seizures. I. Correlation prenatal and perinatal events with outcomes. Pediatrics 1982;7: Mizrahi EM, Kellaway P. Incidence and epidemiology. In: Diagnosis and management neonatal seizures. Philadelphia, PA: Lippincott-Raven Publishers, 1998: Ronen GM, Penny S. Epidemiology clinical neonatal seizures in Newfoundland, Canada: a five-year cohort (Abstract). Epilepsia 1995;36(suppl 3): Lanska MJ, Lanska DJ, Baumann RJ, et al. A population-based study neonatal seizures in Fayette County, Kentucky. Neurology 1995;45: US Department Health and Human Services. International classification diseases, Ninth Revision, clinical modification: ICD-9-CM. 3rd ed. Vol 1. Washington, DC: US GPO, (DHHS publication no. (PHS)89-126). 13. American Academy Pediatrics and American College Obstetricians and Gynecologists. Guidelines for perinatal care. 3rd ed Elk Grove Village, IL: American Academy Pediatrics, Mizrahi EM, Kellaway P. Characterization and classification neonatal seizures. Neurology 1987;37: Cornfield J. A statistical problem arising from retrospective studies. In: Neyman J, ed. Proceedings the Third Berkeley Symposium, vol 4. Berkeley, CA: University California Press, 1956: Stata Corporation. Stata statistical stware, release 5.. College Station, TX: Stata Corporation, Mizrahi EM, Kellaway P. Clinical significance. In: Diagnosis and management neonatal seizures. Philadelphia, PA: Lippincott-Raven Publishers, 1998: Seay AR, Bray PF. Significance seizures in infants weighing less than 2,5 grams. Arch Neurol 1977;34: Bergman I, Painter MJ, Hirsch RP, et al. Outcome in neonates with convulsions treated in an intensive care unit Ann Neurol 1983;14: Watkins A, Szymonowicz W, Jin X, et al. Significance seizures in very low-birthweight infants. Dev Med Child Neurol 1988;3: Hack M, Horbar JD, Malloy MH, et al. Very low birth weight outcomes the National Institute Child Health and Human Development Neonatal Network. Pediatrics 1991;87: Am J Epidemiol Vol. 15, 7, 1999