Slavica K. Katusic

Early Exposure to Anesthesia and Learning Disabilities in a Population-based Birth Cohort

Background:Anesthetic drugs administered to immature animals may cause neurohistopathologic changes and alterations in behavior. The authors studied association between anesthetic exposure before age 4 yr and the development of reading, written language, and math learning disabilities (LD). Methods:This was a population-based, retrospective birth cohort study. The educational and medical records of all children born to mothers residing in five townships of Olmsted County, Minnesota, from 1976 to 1982 and who remained in the community at 5 yr of age were reviewed to identify children with LD. Cox proportional hazards regression was used to calculate hazard ratios for anesthetic exposure as a predictor of LD, adjusting for gestational age at birth, sex, and birth weight. Results:Of the 5,357 children in this cohort, 593 received general anesthesia before age 4 yr. Compared with those not receiving anesthesia (n = 4,764), a single exposure to anesthesia (n = 449) was not associated with an increased risk of LD (hazard ratio = 1.0; 95% confidence interval, 0.79–1.27). However, children receiving two anesthetics (n = 100) or three or more anesthetics (n = 44) were at increased risk for LD (hazard ratio = 1.59; 95% confidence interval, 1.06–2.37, and hazard ratio = 2.60; 95% confidence interval, 1.60–4.24, respectively). The risk for LD increased with longer cumulative duration of anesthesia exposure (expressed as a continuous variable) (P = 0.016). Conclusion:Exposure to anesthesia was a significant risk factor for the later development of LD in children receiving multiple, but not single anesthetics. These data cannot reveal whether anesthesia itself may contribute to LD or whether the need for anesthesia is a marker for other unidentified factors that contribute to LD.

Cognitive and Behavioral Outcomes After Early Exposure to Anesthesia and Surgery

BACKGROUND: Annually, millions of children are exposed to anesthetic agents that cause apoptotic neurodegeneration in immature animals. To explore the possible significance of these findings in children, we investigated the association between exposure to anesthesia and subsequent (1) learning disabilities (LDs), (2) receipt of an individualized education program for an emotional/behavior disorder (IEP-EBD), and (3) scores of group-administered achievement tests. METHODS: This was a matched cohort study in which children (N = 8548) born between January 1, 1976, and December 31, 1982, in Rochester, Minnesota, were the source of cases and controls. Those exposed to anesthesia (n = 350) before the age of 2 were matched to unexposed controls (n = 700) on the basis of known risk factors for LDs. Multivariable analysis adjusted for the burden of illness, and outcomes including LDs, receipt of an IEP-EBD, and the results of group-administered tests of cognition and achievement were outcomes. RESULTS: Exposure to multiple, but not single, anesthetic/surgery significantly increased the risk of developing LDs (hazard ratio: 2.12 [95% confidence interval: 1.26–3.54]), even when accounting for health status. A similar pattern was observed for decrements in group-administered tests of achievement and cognition. However, exposure did not affect the rate of children receiving an individualized education program. CONCLUSIONS: Repeated exposure to anesthesia and surgery before the age of 2 was a significant independent risk factor for the later development of LDs but not the need for educational interventions related to emotion/behavior. We cannot exclude the possibility that multiple exposures to anesthesia/surgery at an early age may adversely affect human neurodevelopment with lasting consequence.

Attention-Deficit/Hyperactivity Disorder After Early Exposure to Procedures Requiring General Anesthesia

OBJECTIVE To study the association between exposure to procedures performed under general anesthesia before age 2 years and development of attention-deficit/hyperactivity disorder (ADHD). PATIENTS AND METHODS Study patients included all children born between January 1, 1976, and December 31, 1982, in Rochester, MN, who remained in Rochester after age 5. Cases of ADHD diagnosed before age 19 years were identified by applying stringent research criteria. Cox proportional hazards regression assessed exposure to procedures requiring general anesthesia (none, 1, 2 or more) as a predictor of ADHD using a stratified analysis with strata based on a propensity score including comorbid health conditions. RESULTS Among the 5357 children analyzed, 341 ADHD cases were identified (estimated cumulative incidence, 7.6%; 95% confidence interval [CI], 6.8%-8.4%). For children with no postnatal exposure to procedures requiring anesthesia before the age of 2 years, the cumulative incidence of ADHD at age 19 years was 7.3% (95% CI, 6.5%-8.1%). For single and 2 or more exposures, the estimates were 10.7% ( 95% CI, 6.8%-14.4%) and 17.9% ( 95% CI, 7.2%-27.4%), respectively. After adjusting for gestational age, sex, birth weight, and comorbid health conditions, exposure to multiple (hazard ratio, 1.95; 95% CI, 1.03-3.71), but not single (hazard ratio,1.18; 95% CI, 0.79-1.77), procedures requiring general anesthesia was associated with an increased risk for ADHD. CONCLUSION Children repeatedly exposed to procedures requiring general anesthesia before age 2 years are at increased risk for the later development of ADHD even after adjusting for comorbidities.

Long-term school outcomes for children with attention-deficit/hyperactivity disorder: a population-based perspective.

Objective: The purpose of this study was to compare long-term school outcomes (academic achievement in reading, absenteeism, grade retention, and school dropout) for children with attention-deficit/hyperactivity disorder (AD/HD) versus those without AD/HD. Methods: Subjects included 370 children with research-identified AD/HD from a 1976–1982 population-based birth cohort (N = 5718) and 740 non-AD/HD control subjects from the same birth cohort, matched by gender and age. All subjects were retrospectively followed from birth until a median age of 18.4 years (AD/HD cases) or 18.3 years (non-AD/HD controls). The complete school record for each subject was reviewed to obtain information on reading achievement (last available California Achievement Test reading score), absenteeism (number/percentage of school days absent at each grade level), grade retention (having to repeat an entire grade in the subsequent school year), and school dropout (failure to graduate from high school). Results: Median reading achievement scores at age 12.8 years (expressed as a national percentile) were significantly different for AD/HD cases and non-AD/HD controls (45 vs 73). Results were similar for both boys and girls with AD/HD. Median percentage of days absent was statistically significantly higher for children with AD/HD versus those without AD/HD, although the difference was relatively small in absolute number of days absent. Subjects with AD/HD were three times more likely to be retained a grade. Similarly, subjects with AD/HD were 2.7 times more likely to drop out before high school graduation (22.9%) than non-AD/HD controls (10.0%). Conclusions: The results of this population-based study clearly demonstrate the association between AD/HD and poor long-term school outcomes.

Epidemiology and Clinical Features of Idiopathic Trigeminal Neuralgia and Glossopharyngeal Neuralgia: Similarities and Differences, Rochester, Minnesota, 1945-1984

A comparison of epidemiological and clinical features of trigeminal neuralgia (TN) and glossopharyngeal neuralgia (GN) in Rochester, Minn., reveals several differences. The overall age- and sex-adjusted annual incidence rates were significantly higher for TN than for GN (4.7 vs. 0.8 per 100,000 population). The TN:GN ratio was increased for both men and women and was 5.9:1 for both sexes combined. This ratio is greater than reported in previous non-population-based studies. GN is a milder disease than TN, as indicated by the number of episodes, treatment, and characterization of pain. The right side is affected more often with TN than with GN. Bilaterality was noted less often in TN than in GN cases.

Incidence of Reading Disability in a Population-Based Birth Cohort, 1976–1982, Rochester, Minn

OBJECTIVE To report the incidence of reading disability among school-aged children. SUBJECTS AND METHODS In this population-based, retrospective birth cohort study, subjects included all 5718 children born between 1976 and 1982 who remained in Rochester, Minn, after the age of 5 years. Based on records from all public and nonpublic schools, medical facilities, and private tutorial services and on results of all individually administered IQ and achievement tests, extensive medical, educational, and socioeconomic information were abstracted. Reading disability was established with use of research criteria based on 4 formulas (2 regression-based discrepancy, 1 non-regression-based discrepancy, and 1 low achievement). RESULTS Cumulative incidence rates of reading disability varied from 5.3% to 11.8% depending on the formula used. Boys were 2 to 3 times more likely to be affected than girls, regardless of the identification methods applied. CONCLUSIONS In this population-based birth cohort, reading disability was common among school-aged children and significantly more frequent among boys than girls, regardless of definition.

Math learning disorder: incidence in a population-based birth cohort, 1976-82, Rochester, Minn.

OBJECTIVE To report the incidence of math learning disorder (Math LD) among school-aged children, overall and by gender. To compare incidence estimates obtained by using three different methods to identify Math LD cases. To assess the extent to which children manifest Math LD alone, versus Math LD with comorbid reading disorder. METHODS This is a population-based, retrospective, birth cohort study. Subjects included all children born 1976-82 who remained in Rochester, Minn after age 5 (N = 5718). Using records from all public and private schools, medical facilities, and private tutorial services, all individually administered intelligence quotient and achievement tests and extensive medical, educational, and socioeconomic information were abstracted. Math LD was established using research criteria based on 3 formulas (regression-based discrepancy, nonregression-based discrepancy, low achievement). RESULTS Cumulative incidence rates of Math LD by age 19 years varied from 5.9% to 13.8% according to the formula used. Boys were more likely to be affected than girls, with relative risk ratios from 1.6 to 2.2 depending on the formula applied. Many children with Math LD (35% to 56.7%, depending on the formula used to define Math LD) did not have a comorbid reading disorder. CONCLUSIONS These results, from a community-based birth cohort, suggest that Math LD is common among schoolchildren, and is significantly more frequent among boys than girls, regardless of definition. Many children with Math LD do not have an associated reading disorder.

Incidence of Gastrointestinal Symptoms in Children With Autism: A Population-Based Study

OBJECTIVE: To determine whether children with autism have an increased incidence of gastrointestinal symptoms compared with matched control subjects in a population-based sample. DESIGN/METHODS: In a previous study including all of the residents of Olmsted County, Minnesota, aged <21 years between 1976 and 1997, we identified 124 children who fulfilled criteria on the basis of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, for a research diagnosis of autism. Two matched control subjects were identified for each case subject. Through the Rochester Epidemiology Project, all medical diagnoses, are indexed for computerized retrieval. Gastrointestinal diagnoses before 21 years of age were grouped into 5 categories: (1) constipation; (2) diarrhea; (3) abdominal bloating, discomfort, or irritability; (4) gastroesophageal reflux or vomiting; and (5) feeding issues or food selectivity. The cumulative incidence of each category was calculated by using the Kaplan-Meier method. Cox proportional hazards models were fit to estimate the risk ratios (case subjects versus control subjects) and corresponding 95% confidence intervals. RESULTS: Subjects were followed to median ages of 18.2 (case subjects) and 18.7 (control subjects) years. Significant differences between autism case and control subjects were identified in the cumulative incidence of constipation (33.9% vs 17.6%) and feeding issues/food selectivity (24.5% vs 16.1). No significant associations were found between autism case status and overall incidence of gastrointestinal symptoms or any other gastrointestinal symptom category. CONCLUSIONS: As constipation and feeding issues/food selectivity often have a behavioral etiology, data suggest that a neurobehavioral rather than a primary organic gastrointestinal etiology may account for the higher incidence of these gastrointestinal symptoms in children with autism.

Mortality, ADHD, and Psychosocial Adversity in Adults With Childhood ADHD: A Prospective Study

OBJECTIVE: We examined long-term outcomes of attention-deficit/hyperactivity disorder (ADHD) in a population-based sample of childhood ADHD cases and controls, prospectively assessed as adults. METHODS: Adults with childhood ADHD and non-ADHD controls from the same birth cohort (N = 5718) were invited to participate in a prospective outcome study. Vital status was determined for birth cohort members. Standardized mortality ratios (SMRs) were constructed to compare overall and cause-specific mortality between childhood ADHD cases and controls. Incarceration status was determined for childhood ADHD cases. A standardized neuropsychiatric interview was administered. RESULTS: Vital status for 367 childhood ADHD cases was determined: 7 (1.9%) were deceased, and 10 (2.7%) were currently incarcerated. The SMR for overall survival of childhood ADHD cases versus controls was 1.88 (95% confidence interval [CI], 0.83–4.26; P = .13) and for accidents only was 1.70 (95% CI, 0.49–5.97; P = .41). However, the cause-specific mortality for suicide only was significantly higher among ADHD cases (SMR, 4.83; 95% CI, 1.14–20.46; P = .032). Among the childhood ADHD cases participating in the prospective assessment (N = 232; mean age, 27.0 years), ADHD persisted into adulthood for 29.3% (95% CI, 23.5–35.2). Participating childhood ADHD cases were more likely than controls (N = 335; mean age, 28.6 years) to have ≥1 other psychiatric disorder (56.9% vs 34.9%; odds ratio, 2.6; 95% CI, 1.8–3.8; P < .01). CONCLUSIONS: Childhood ADHD is a chronic health problem, with significant risk for mortality, persistence of ADHD, and long-term morbidity in adulthood.

Anesthesia for Cesarean Delivery and Learning Disabilities in a Population-Based Birth Cohort

Background:Anesthetics administered to immature brains may cause histopathological changes and long-term behavioral abnormalities. The association between perinatal exposure to anesthetics during Cesarean delivery (CD) and development of learning disabilities (LD) was determined in a population-based birth cohort. Methods:The educational and medical records of all children born to mothers residing in five townships of Olmsted County, Minnesota from 1976–1982 and remaining in the community at age 5 were reviewed to identify those with LDs. Cox proportional hazards regression was used to compare rates of LD between children delivered vaginally and via CD (with general or regional anesthesia). Results:Of the 5,320 children in this cohort, 497 were delivered via CD (under general anesthesia n = 193, and regional anesthesia n = 304). The incidence of LD depended on mode of delivery (P = 0.050, adjusted for sex, birth weight, gestational age, exposure to anesthesia before age 4 yr, and maternal education). LD risk was similar in children delivered by vagina or CD with general anesthesia, but was reduced in children receiving CD with regional anesthesia (hazard ratio = 0.64, 95% confidence interval 0.44 to 0.92; P = 0.017 for comparison of CD under regional anesthesia compared to vaginal delivery). Conclusion:Children exposed to general or regional anesthesia during CD are not more likely to develop LD compared to children delivered vaginally, suggesting that brief perinatal exposure to anesthetic drugs does not adversely affect long-term neurodevelopmental outcomes. The risk of LD may be lower in children delivered by CD whose mothers received regional anesthesia.