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ABSTRACT: Valproate is used for the treatment of epilepsy and other neuropsychological disorders and may be the only treatment option for women of childbearing potential. However, prenatal exposure to valproate may increase the risk of autism.
To determine whether prenatal exposure to valproate is associated with an increased risk of autism in offspring.
Population-based study of all children born alive in Denmark from 1996 to 2006. National registers were used to identify children exposed to valproate during pregnancy and diagnosed with autism spectrum disorders (childhood autism [autistic disorder], Asperger syndrome, atypical autism, and other or unspecified pervasive developmental disorders). We analyzed the risks associated with all autism spectrum disorders as well as childhood autism. Data were analyzed by Cox regression adjusting for potential confounders (maternal age at conception, paternal age at conception, parental psychiatric history, gestational age, birth weight, sex, congenital malformations, and parity). Children were followed up from birth until the day of autism spectrum disorder diagnosis, death, emigration, or December 31, 2010, whichever came first. MAIN OUTCOMES AND MEASURES: Absolute risk (cumulative incidence) and the hazard ratio (HR) of autism spectrum disorder and childhood autism in children after exposure to valproate in pregnancy.
Of 655,615 children born from 1996 through 2006, 5437 were identified with autism spectrum disorder, including 2067 with childhood autism. The mean age of the children at end of follow-up was 8.84 years (range, 4-14; median, 8.85). The estimated absolute risk after 14 years of follow-up was 1.53% (95% CI, 1.47%-1.58%) for autism spectrum disorder and 0.48% (95% CI, 0.46%-0.51%) for childhood autism. Overall, the 508 children exposed to valproate had an absolute risk of 4.42% (95% CI, 2.59%-7.46%) for autism spectrum disorder (adjusted HR, 2.9 [95% CI, 1.7-4.9]) and an absolute risk of 2.50% (95% CI, 1.30%-4.81%) for childhood autism (adjusted HR, 5.2 [95% CI, 2.7-10.0]). When restricting the cohort to the 6584 children born to women with epilepsy, the absolute risk of autism spectrum disorder among 432 children exposed to valproate was 4.15% (95% CI, 2.20%-7.81%) (adjusted HR, 1.7 [95% CI, 0.9-3.2]), and the absolute risk of childhood autism was 2.95% (95% CI, 1.42%-6.11%) (adjusted HR, 2.9 [95% CI, 1.4-6.0]) vs 2.44% (95% CI, 1.88%-3.16%) for autism spectrum disorder and 1.02% (95% CI, 0.70%-1.49%) for childhood autism among 6152 children not exposed to valproate.
Maternal use of valproate during pregnancy was associated with a significantly increased risk of autism spectrum disorder and childhood autism in the offspring, even after adjusting for maternal epilepsy. For women of childbearing potential who use antiepileptic medications, these findings must be balanced against the treatment benefits for women who require valproate for epilepsy control.
JAMA The Journal of the American Medical Association 04/2013; 309(16):1696-703. · 30.03 Impact Factor
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Girija Natarajan,
Seetha Shankaran,
Scott A McDonald,
Abhik Das,
Richard A Ehrenkranz,
Ronald N Goldberg,
Barbara J Stoll,
Jon E Tyson,
Rosemary D Higgins, Diana Schendel,
David M Hougaard,
Kristin Skogstrand,
Poul Thorsen,
Waldemar A Carlo
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ABSTRACT: Permanent ductal closure involves anatomic remodeling, in which transforming growth factor (TGF)-β appears to play a role. Our objective was to evaluate the relationship, if any, between blood spot TGF-β on day 3 and day 7 of life and patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants. Prospective observational study involving ELBW infants (n = 968) in the National Institute of Child Health and Human Development Neonatal Research Network who had TGF-β measured on filter paper spot blood samples using a Luminex assay. Infants with a PDA (n = 493) were significantly more immature, had lower birth weights, and had higher rates of respiratory distress syndrome than those without PDA (n = 475). TGF-β on days 3 and 7 of life, respectively, were significantly lower among neonates with PDA (median 1,177 pg/ml [range 642-1,896]; median 1,386 pg/ml [range 868-1,913]) compared with others without PDA (median 1,334 pg/ml [range 760-2,064]; median 1,712 pg/ml [range 1,014-2,518 pg/ml]). The significant difference persisted when death or PDA was considered a composite outcome. TGF-β levels were not significantly different among subgroups of infants with PDA who were not treated (n = 51) versus those who were treated medically (n = 283) or by surgical ligation (n = 159). TGF-β was not a significant predictor of death or PDA (day 3 odds ratio [OR] 0.99, 95 % confidence interval [CI] 0.83-1.17; day 7 OR 0.88, 95 % CI 0.74-1.04) on adjusted analyses. Our results suggest that blood spot TGF-β alone is unlikely to be a reliable biomarker of a clinically significant PDA or its responsiveness to treatment.
Pediatric Cardiology 06/2012; · 1.30 Impact Factor
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Waldemar A Carlo,
Scott A McDonald,
Jon E Tyson,
Barbara J Stoll,
Richard A Ehrenkranz,
Seetha Shankaran,
Ronald N Goldberg,
Abhik Das, Diana Schendel,
Poul Thorsen, [......],
Edward F Donovan,
Sheldon B Korones,
David K Stevenson,
Lu-Ann Papile,
Neil N Finer,
T Michael O'Shea,
Brenda B Poindexter,
Linda L Wright,
Namasivayam Ambalavanan,
Rosemary D Higgins
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ABSTRACT: To determine if selected pro-inflammatory and anti-inflammatory cytokines and/or mediators of inflammation reported to be related to the development of cerebral palsy (CP) predict neurodevelopmental outcome in extremely low birth weight infants.
Infants with birth weights ≤1000 g (n = 1067) had blood samples collected at birth and on days 3 ± 1, 7 ± 1, 14 ± 3, and 21 ± 3 to examine the association between cytokines and neurodevelopmental outcomes. The analyses were focused on 5 cytokines (interleukin [IL] 1β; IL-8; tumor necrosis factor-α; regulated upon activation, normal T-cell expressed, and secreted (RANTES); and IL-2) reported to be most predictive of CP in term and late preterm infants.
IL-8 was higher on days 0-4 and subsequently in infants who developed CP compared with infants who did not develop CP in both unadjusted and adjusted analyses. Other cytokines (IL-12, IL-17, tumor necrosis factor-β, soluble IL rα, macrophage inflammatory protein 1β) were found to be altered on days 0-4 in infants who developed CP.
CP in former preterm infants may, in part, have a late perinatal and/or early neonatal inflammatory origin.
The Journal of pediatrics 07/2011; 159(6):919-25.e3. · 4.02 Impact Factor
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ABSTRACT: Fetal and neonatal inflammation is associated with several morbidities of prematurity. Its relationship to retinopathy of prematurity (ROP) has not been investigated. Our objective was to determine the relationship between cytokine levels and ROP in the first 3 postnatal wks. Data for this study were derived from the NICHD Cytokine Study. Dried blood spots (DBS) were obtained from infants <1000 g on days 0-1, 3 +/- 1, 7 +/- 2, 14 +/- 3, and 21 +/- 3. Infants were classified into three groups-no, mild, and severe ROP. Multiplex Luminex assay was used to quantify 20 cytokines. Temporal profiles of cytokines were evaluated using mixed-effects models after controlling for covariates. Of 1074 infants enrolled, 890 were examined for ROP and 877 included in the analysis. ROP was associated with several clinical characteristics on unadjusted analyses. Eight cytokines remained significantly different across ROP groups in adjusted analyses. IL-6 and IL-17 showed significant effects in early time periods (D0-3); TGF-beta, brain-derived neurotrophic factor (BDNF), and regulated on activation, normal T cell expressed and secreted (RANTES) in later time periods (D7-21) and IL-18, C-reactive protein (CRP), and neurotrophin-4 (NT-4) in both early and later time periods. We conclude that perinatal inflammation may be involved in the pathogenesis of ROP.
Pediatric Research 04/2010; 67(4):394-400. · 2.70 Impact Factor
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Ulrik Schiøler Kesmodel,
Mette Underbjerg,
Tina Røndrup Kilburn,
Leiv Bakketeig,
Erik Lykke Mortensen,
Nils Inge Landrø, Diana Schendel,
Jacquelyn Bertrand,
Jakob Grove,
Shahul Ebrahim,
Poul Thorsen
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ABSTRACT: It has been suggested that even mild exposure to alcohol, caffeine, smoking, and poor diet may have adverse long-term neurodevelopmental effects. In addition, there is evidence that timing of high exposures (e.g. binge drinking) can have particularly negative effects. This paper describes the design and implementation of The Lifestyle During Pregnancy Study addressing major methodological challenges for studies in this field. The study examines the effects of lifestyle during pregnancy on offspring neurodevelopment.
In 2003, we initiated a prospective follow-up of 1750 mother-child pairs, sampled on the basis of maternal alcohol drinking patterns from The Danish National Birth Cohort (DNBC), a study of 101,042 pregnancies enrolled 1997-2003. Data collection in the DNBC involved four prenatal and postnatal maternal interviews, providing detailed information on maternal alcohol drinking patterns before and during pregnancy, caffeine intake, smoking, diet, and other lifestyle, medical, and sociodemographic factors.
At the age of 5 years, the children and their mothers participated in a comprehensive assessment of neurobehavioural development focusing on global cognition, specific cognitive functions, and behaviour. Two new tests assessing attention and speed of information processing among children were developed, and data on important potential confounders such as maternal intelligence quotient, vision, and hearing abilities were collected. Efforts were made to standardise procedures and obtain high inter-rater reliability.
We expect that the study will illuminate the significance or lack of significance of maternal lifestyle during pregnancy and contribute to better understanding the effects of alcohol drinking during pregnancy at low to moderate consumption levels.
Scandinavian Journal of Public Health 03/2010; 38(2):208-19. · 1.39 Impact Factor
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ABSTRACT: The purpose of this study was to assess the validity of the diagnosis of childhood autism in the Danish Psychiatric Central Register (DPCR) by reviewing medical records from 499 of 504 total children with childhood autism born 1990-1999. Based on review of abstracted behaviors recorded in case records from child psychiatric hospitals, case status determination was performed using a standardized coding scheme. In 499 children diagnosed with childhood autism in the DPCR, the diagnosis could be confirmed in 469 children (94%). Of the 30 non-confirmed cases, five were classified by the reviewers as non-autistic cases and the remaining 25 cases were either classified with another ASD diagnosis or the specific diagnosis was not possible to determine.
Journal of Autism and Childhood Schizophrenia 10/2009; 40(2):139-48. · 3.06 Impact Factor
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ABSTRACT: The goal was to develop multivariate logistic regression models for the outcome of bronchopulmonary dysplasia and/or death at postmenstrual age of 36 weeks by using clinical and cytokine data from the first 28 days.
For 1067 extremely low birth weight infants in the Neonatal Research Network of the National Institute of Child Health and Human Development, levels of 25 cytokines were measured in blood collected within 4 hours after birth and on days 3, 7, 14, and 21. Stepwise regression analyses using peak levels of the 25 cytokines and 15 clinical variables identified variables associated with bronchopulmonary dysplasia/death. Multivariate logistic regression analysis was performed for bronchopulmonary dysplasia/death by using variables selected through stepwise regression. Similar analyses were performed by using average cytokine values from days 0 to 21, days 0 to 3, and days 14 to 21.
Of 1062 infants with available data, 606 infants developed bronchopulmonary dysplasia or died. On the basis of results from all models combined, bronchopulmonary dysplasia/death was associated with higher concentrations of interleukin 1beta, 6, 8, and 10 and interferon gamma and lower concentrations of interleukin 17, regulated on activation, normal T cell expressed and secreted, and tumor necrosis factor beta. Compared with models with only clinical variables, the addition of cytokine data improved predictive ability by a statistically significant but clinically modest magnitude.
The overall cytokine pattern suggests that bronchopulmonary dysplasia/death may be associated with impairment in the transition from the innate immune response mediated by neutrophils to the adaptive immune response mediated by T lymphocytes.
PEDIATRICS 05/2009; 123(4):1132-41. · 4.47 Impact Factor
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ABSTRACT: To assess the existing evidence of associations between assisted conception and cerebral palsy (CP), autism spectrum disorders (ASD), and developmental delay.
Forty-one studies identified in a systematical PubMed and Excerpta Medica Database (EMBASE) search for articles published from January 1, 1996, to April 1, 2008.
Studies written in English comparing children born after assisted conception with children born after natural conception assessing CP, ASD, and developmental delay, based on original data with a follow-up of 1 year or more. Main Exposures In vitro fertilization (IVF) with or without intracytoplasmic sperm injection or ovulation induction with or without subsequent intrauterine insemination.
Cerebral palsy, ASD, and developmental delay.
Nine CP studies showed that children born after IVF had an increased risk of CP associated with preterm delivery. In our meta-analysis including 19 462 children exposed to IVF, we estimated a crude odds ratio of 2.18 (95% confidence interval, 1.71-2.77). Eight ASD studies and 30 studies on developmental delay showed inconsistent results. No studies assessed the risk of CP, ASD, or developmental delay in children born after ovulation induction exclusively.
Methodological problems were revealed in the identified studies, and the gaps in our knowledge about the long-term outcomes of children born after assisted conception are considerable, including a lack of information on the long-term consequences of ovulation induction. Possible associations with ASD and developmental delay need assessment in larger studies. Studies on assisted conception and CP from countries outside of Scandinavia are needed, including detailed information on time to pregnancy, underlying cause of infertility, and type of IVF treatment.
Archives of pediatrics & adolescent medicine 02/2009; 163(1):72-83. · 3.73 Impact Factor
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ABSTRACT: To examine associations between first-trimester plasma cytokines and spontaneous preterm delivery (sPTD).
A case-control study was nested within the Danish National Birth Cohort, a cohort of women with 101,042 pregnancies from 1997 to 2002 who were recruited during pregnancy and followed prospectively.
Subjects included 107 women delivering singleton infants at 24-29 weeks, 353 at 30-33 weeks, 422 at 34-36 weeks, and 1,372 at > or =37 weeks.
Maternal plasma interleukin (IL)-2, IL-6, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured at a median of eight weeks gestation using multiplex flow cytometry. Adjusted odds ratios (ORs) were obtained using polytomous logistic regression.
sPTD categorized as: 24-29 weeks, 30-33 weeks, 34-36 weeks, and > or =37 weeks (controls).
Elevated TNF-alpha and GM-CSF were associated with an increased risk of delivery at 34-36 weeks. In underweight women, sPTD <34 weeks was associated with elevated (>75th percentile) IL-6 (OR=5.62, 95% confidence interval (CI): 1.73, 18.26) and TNF-alpha (OR=3.02, CI: 1.02, 8.91) compared with term delivery. Conversely, among obese women, elevated IL-2 (OR=0.30, CI: 0.11, 0.78) and TNF-alpha (OR=0.15, CI: 0.05, 0.47) were associated with a reduced risk of delivering at <34 weeks. Cytokines were not related to delivery at <34 weeks in normal-weight and overweight women.
These findings suggest that the association between first-trimester plasma cytokine levels and sPTD may depend on pre-pregnancy body mass index.
Acta Obstetricia Et Gynecologica Scandinavica 02/2009; 88(3):332-42. · 1.77 Impact Factor
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ABSTRACT: A higher risk of meningitis associated with cochlear implants may be explained in part by a generally higher risk of meningitis in children with severe to profound hearing loss. We investigated whether children with hearing loss have an increased risk of meningitis.
A historical cohort study of all children born in Denmark between January 1, 1995, and December 31, 2004, was conducted. The cohort was selected through the Danish Medical Birth Registry, and information on hearing loss and meningitis was obtained from the National Hospital Registry.
We identified 39 children with both hearing loss and meningitis. Of these children, five were diagnosed first with hearing loss and later with meningitis. The relative risk of meningitis in the group of children with a hearing loss diagnosis, as compared with the non-hearing loss group, was 5.0 (95% CI, 2.0 to 12.0).
The study provides evidence for an association between hearing loss and the development of meningitis. Parents and health care providers of children with hearing loss should be more alert for possible signs and symptoms of meningitis, and vaccination should be considered.
Otolaryngology Head and Neck Surgery 04/2007; 136(3):428-33. · 1.72 Impact Factor
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ABSTRACT: The etiologies of autism spectrum disorder and many neurodevelopmental disorders are largely unknown. The detection of a seasonal variation of birth of children diagnosed with a certain disorder could suggest etiological factors that follow a seasonal pattern. We examined the seasonal variation of births of children diagnosed with any of 4 common childhood neuropsychiatric disorders: autism spectrum disorder, hyperkinetic disorder, Tourette syndrome, and obsessive-compulsive disorder.
The study cohort consisted of all children born in Denmark from 1990 through 1999 identified in the Danish Medical Birth Register (n = 669,995). Outcome data consisted of both inpatient and outpatient diagnoses reported to the Danish National Psychiatric Registry from 1995 through 2004 using the International Classification of Diseases, 10th edition, diagnostic coding system. Logistic regression combined with spline (a smoothing method) was used to estimate the variation with season of birth for each disorder. Estimates of risk of each disorder with season of birth were adjusted for differences in follow-up time and change in incidence over time.
No convincing variations in season of birth were observed for any of the 4 disorders, or for the autism-spectrum-disorder subtypes.
Although we cannot rule out the possibility of seasonal variation of birth for a range of childhood neurodevelopmental disorders, we find little evidence that seasonal environmental factors are related to these disorders.
Epidemiology 04/2007; 18(2):240-5. · 5.57 Impact Factor
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ABSTRACT: To examine trends in autism (autism spectrum disorder and childhood autism) in the context of 3 additional childhood neuropsychiatric disorders: hyperkinetic disorder, Tourette syndrome, and obsessive-compulsive disorder.
Population-based cohort study.
Children were identified in the Danish Medical Birth Registry. Relevant outcomes were obtained via linkage with the Danish National Psychiatric Register, which included reported diagnoses through 2004 by psychiatrists using diagnostic criteria from the International Statistical Classification of Diseases, 10th Revision.
All children born in Denmark from 1990 through 1999, a total of 669 995 children.
Cumulative incidence proportion by age, stratified by year of birth, for each disorder.
Statistically significant increases were found in cumulative incidence across specific birth years for autism spectrum disorder, childhood autism, hyperkinetic disorder, and Tourette syndrome. No significant change in cumulative incidence was observed for obsessive-compulsive disorder.
Recent increases in reported autism diagnoses might not be unique among childhood neuropsychiatric disorders and might be part of a more widespread epidemiologic phenomenon. The reasons for the observed common pattern of change in reported cumulative incidence could not be determined in this study, but the data underscore the growing awareness of and demand for services for children with neurodevelopmental disorders in general.
Archives of Pediatrics and Adolescent Medicine 03/2007; 161(2):193-8. · 4.14 Impact Factor
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ABSTRACT: Few studies have investigated the relationship between inflammation and spontaneous preterm delivery (sPTD) in women before preterm labour. The authors examine whether mid-pregnancy plasma cytokine levels are associated with sPTD, and whether associations vary by maternal age, body mass index, prior preterm delivery, or gravidity.
This case-control study was nested within the Danish National Birth Cohort, a cohort of women with 101,042 pregnancies from 1997 to 2002. Included in this study are 61 women delivering at 24-29 weeks, 278 delivering at 30-33 weeks, 334 delivering at 34-36 weeks, and 1,125 delivering at > or =37 weeks. Maternal plasma interleukin (IL)-2, IL-6, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and granulocyte-macrophage colony-stimulating factor (GM-CSF) at 25 weeks' gestation were measured using multiplex flow cytometry.
For IL-2, TNF-alpha, and GM-CSF, the proportion of women with levels >75th or >90th percentile did not differ by gestational age at delivery. IFN-gamma >90th percentile was associated with an increased risk of delivering at 30-33 weeks (crude odds ratio (cOR): 1.56; 95% confidence interval (CI): 1.07-2.30), while IFN-gamma >75th percentile and IL-6 >75th percentile were associated with an increased risk of delivering at 34-36 weeks (cOR: 1.32; 95% CI: 1.01-1.73); estimates changed little after adjusting for confounders. There was no effect-measure modification by maternal factors.
Elevated mid-pregnancy plasma IL-2, TNF-alpha, and GM-CSF did not appear to be associated with an increased risk of sPTD, while elevated IFN-gamma and IL-6 levels were weakly associated with moderate and late sPTD. The value of using mid-pregnancy cytokines in predicting spontaneous preterm delivery appears limited.
Acta Obstetricia Et Gynecologica Scandinavica 01/2007; 86(9):1103-10. · 1.77 Impact Factor
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ABSTRACT: In a Danish population-based cohort study assessing the risk of cerebral palsy in children born after IVF, we made some interesting observations regarding 'vanishing co-embryos'. METHODS and
All live-born children born in Denmark from 1 January 1995 to 31 December 2000 were included in this analysis. The children conceived by IVF/ICSI (9444) were identified through the IVF Register, the children conceived without IVF/ICSI (395 025) were identified through The Danish Medical Birth Register. Main outcome measure was the incidence of cerebral palsy. Within the IVF/ICSI children we found indications of an increased risk of cerebral palsy in those children resulting from pregnancies, where the number of embryos transferred was higher than the number of children born.
The association between vanishing embryo syndrome and incidence of cerebral palsy following IVF requires further investigation in larger, adequately powered, studies.
Human Reproduction 10/2005; 20(9):2550-1. · 4.47 Impact Factor
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ABSTRACT: Research suggests that heredity and early fetal development play a causal role in autism. This case-control study explored the association between perinatal factors, parental psychiatric history, socioeconomic status, and risk of autism. The study was nested within a cohort of all children born in Denmark after 1972 and at risk of being diagnosed with autism until December 1999. Prospectively recorded data were obtained from nationwide registries in Denmark. Cases totaled 698 children with a diagnosis of autism; each case was individually matched by gender, birth year, and age to 25 controls. Analyses by conditional logistic regression produced risk ratios and 95% confidence intervals. Adjusted analyses showed that the risk of autism was associated with breech presentation (risk ratio (RR) = 1.63, 95% confidence interval (CI): 1.18, 2.26), low Apgar score at 5 minutes (RR = 1.89, 95% CI: 1.10, 3.27), gestational age at birth <35 weeks (RR = 2.45, 95% CI: 1.55, 3.86), and parental psychiatric history (schizophrenia-like psychosis: RR = 3.44, 95% CI: 1.48, 7.95; affective disorder: RR = 2.91, 95% CI: 1.65, 5.14). Analyses showed no statistically significant association between risk of autism and weight for gestational age, parity, number of antenatal visits, parental age, or socioeconomic status. Results suggest that prenatal environmental factors and parental psychopathology are associated with the risk of autism. These factors seem to act independently.
American Journal of Epidemiology 05/2005; 161(10):916-25; discussion 926-8. · 5.22 Impact Factor
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ABSTRACT: The rate of febrile seizures increases following measles, mumps, and rubella (MMR) vaccination but it is unknown whether the rate varies according to personal or family history of seizures, perinatal factors, or socioeconomic status. Furthermore, little is known about the long-term outcome of febrile seizures following vaccination.
To estimate incidence rate ratios (RRs) and risk differences of febrile seizures following MMR vaccination within subgroups of children and to evaluate the clinical outcome of febrile seizures following vaccination.
A population-based cohort study of all children born in Denmark between January 1, 1991, and December 31, 1998, who were alive at 3 months; 537,171 children were followed up until December 31, 1999, by using data from the Danish Civil Registration System and 4 other national registries.
Incidence of first febrile seizure, recurrent febrile seizures, and subsequent epilepsy.
A total of 439,251 children (82%) received MMR vaccination and 17,986 children developed febrile seizures at least once; 973 of these febrile seizures occurred within 2 weeks of MMR vaccination. The RR of febrile seizures increased during the 2 weeks following MMR vaccination (2.75; 95% confidence interval [CI], 2.55-2.97), and thereafter was close to the observed RR for nonvaccinated children. The RR did not vary significantly in the subgroups of children that had been defined by their family history of seizures, perinatal factors, or socioeconomic status. At 15 to 17 months, the risk difference of febrile seizures within 2 weeks following MMR vaccination was 1.56 per 1000 children overall (95% CI, 1.44-1.68), 3.97 per 1000 (95% CI, 2.90-5.40) for siblings of children with a history of febrile seizures, and 19.47 per 1000 (95% CI, 16.05-23.55) for children with a personal history of febrile seizures. Children with febrile seizures following MMR vaccinations had a slightly increased rate of recurrent febrile seizures (RR, 1.19; 95% CI, 1.01-1.41) but no increased rate of epilepsy (RR, 0.70; 95% CI, 0.33-1.50) compared with children who were nonvaccinated at the time of their first febrile seizure.
MMR vaccination was associated with a transient increased rate of febrile seizures but the risk difference was small even in high-risk children. The long-term rate of epilepsy was not increased in children who had febrile seizures following vaccination compared with children who had febrile seizures of a different etiology.
JAMA The Journal of the American Medical Association 08/2004; 292(3):351-7. · 30.03 Impact Factor
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ABSTRACT: It has been suggested that the measles-mumps-rubella (MMR) vaccination causes autism.
We conducted a retrospective cohort study of all children born in Denmark from January 1991 through December 1998. The cohort was established based on data from the Danish Civil Registration System. A unique person identifiable number given to all subjects enabled linkage with other national registries. MMR vaccination status was obtained from the Danish National Board of Health. Information on the children's autism status was obtained from the Danish Psychiatric Central Register which contains information on all diagnoses received from psychiatric hospitals, psychiatric wards, and outpatient clinics in Denmark. We obtained information on potential confounders from the Danish Medical Birth Registry, the National Hospital Registry, and Statistics Denmark.
In the cohort of 537,303 children (2,129,864 person-years), 440,655 children had been MMR vaccinated. We identified 316 children with a diagnosis of autistic disorder and 442 with a diagnosis of other spectrum disorders. After adjusting for potential confounders, the risk for autistic disorder and other spectrum disorders was not increased in vaccinated compared with unvaccinated children (relative risk 0.92; 95 percent confidence interval, 0.68 to 1.24 and relative risk 0.83; 95 percent confidence interval, 0.65 to 1.07). There was no association between age at vaccination, time since vaccination or calendar period at time of vaccination and development of autistic disorder.
This study provides strong evidence against the hypothesis that MMR vaccination causes autism.
Ugeskrift for laeger 01/2003; 164(49):5741-4.
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ABSTRACT: It has been suggested that vaccination against measles, mumps, and rubella (MMR) is a cause of autism.
We conducted a retrospective cohort study of all children born in Denmark from January 1991 through December 1998. The cohort was selected on the basis of data from the Danish Civil Registration System, which assigns a unique identification number to every live-born infant and new resident in Denmark. MMR-vaccination status was obtained from the Danish National Board of Health. Information on the children's autism status was obtained from the Danish Psychiatric Central Register, which contains information on all diagnoses received by patients in psychiatric hospitals and outpatient clinics in Denmark. We obtained information on potential confounders from the Danish Medical Birth Registry, the National Hospital Registry, and Statistics Denmark.
Of the 537,303 children in the cohort (representing 2,129,864 person-years), 440,655 (82.0 percent) had received the MMR vaccine. We identified 316 children with a diagnosis of autistic disorder and 422 with a diagnosis of other autistic-spectrum disorders. After adjustment for potential confounders, the relative risk of autistic disorder in the group of vaccinated children, as compared with the unvaccinated group, was 0.92 (95 percent confidence interval, 0.68 to 1.24), and the relative risk of another autistic-spectrum disorder was 0.83 (95 percent confidence interval, 0.65 to 1.07). There was no association between the age at the time of vaccination, the time since vaccination, or the date of vaccination and the development of autistic disorder.
This study provides strong evidence against the hypothesis that MMR vaccination causes autism.
New England Journal of Medicine 12/2002; 347(19):1477-82. · 53.30 Impact Factor
