Identifying children with autism spectrum disorder at 18 months in a general population sample.

BACKGROUND: Previous research on clinical and high-risk samples suggests that signs of autism spectrum disorder (ASD) can be detected between 1 and 2 years of age. We investigated signs of ASD at 18 months in a population-based sample and the association with later ASD diagnosis. METHODS: The study sample includes 52,026 children born 2003 through 2008 and is a subset of children that participated in the Norwegian Mother and Child Cohort (MoBa), a population-based longitudinal study, and the Autism Birth Cohort (ABC), a sub-study on ASD. Parents completed all 23 items from the Modified Checklist for Autism in Toddlers (M-CHAT) at 18 months. RESULTS: The M-CHAT 6-critical-item criterion and the 23-item criterion had a specificity of 97.9% and 92.7% and a sensitivity of 20.8% and 34.1%, respectively. In the 173 children diagnosed with ASD to date, 60 children (34.7%) scored above the cut-off on either of the screening criteria. The items with the highest likelihood ratios were 'interest in other children', 'show objects to others' and 'response to name'. CONCLUSION: Even though one-third of the children who later received an ASD diagnosis were identified through M-CHAT items, the majority scored below cut-off on the screening criteria at 18 months. The results imply that it might not be possible to detect all children with ASD at this age.

Important periods of weight development in childhood: a population-based longitudinal study.

BACKGROUND: Identifying important ages for the development of overweight is essential for optimizing preventive efforts. The purpose of the study was to explore early growth characteristics in children who become overweight or obese at the age of 8 years to identify important ages for the onset of overweight and obesity. METHODS: Data from the Norwegian Child Growth Study in 2010 (N = 3172) were linked with repeated measurements from health records beginning at birth. Weight and height were used to derive the body mass index (BMI) in kg/m2. The BMI standard deviation score (SDS) for each participant was estimated at specific target ages, using a piecewise linear mixed effect model. RESULTS: At 8 years of age, 20.4% of the children were overweight or obese. Already at birth, overweight children had a significantly higher mean BMI SDS than normal weight 8-year-olds (p < .001) and this difference increased in consecutive age groups in infancy and childhood. A relatively large increase in BMI during the first 9 months was identified as important for being overweight at 8 years. BMI SDS at birth was associated with overweight at 8 years of age (OR, 1.8; 1.6-2.0), and with obesity (OR, 1.8; 1.4-2.3). The Odds Ratios for the BMI SDS and change in BMI SDS further increased up to 1 year of age became very high from 2 years of age onwards. CONCLUSIONS: A high birth weight and an increasing BMI SDS during the first 9 months and high BMI from 2 years of age proved important landmarks for the onset of being overweight at 8 years of age. The risks of being overweight at 8 years appear to start very early. Interventions to prevent children becoming overweight should not only start at a very early age but also include the prenatal stage.

ESAT and M-CHAT as screening instruments for autism spectrum disorders at 18 months in the general population: issues of overlap and association with clinical referrals.

The Modified Checklist for Autism in Toddlers (M-CHAT) and the Early Screening of Autistic Traits (ESAT) were designed to screen for autism spectrum disorders in very young children. The aim of this study was to explore proportions of children that screened positive on the ESAT or the M-CHAT and to investigate if screening positive on the ESAT and M-CHAT is associated with clinical referral by 18 months and other aspects of children's development, health, and behavior. In this study, the mothers of 12,948 18-month-old children returned a questionnaire consisting of items from the ESAT and M-CHAT, plus questions about clinical and developmental characteristics. The M-CHAT identified more screen-positive children than the ESAT, but the ESAT was associated with more clinical referrals and tended to identify more children with medical, language, and behavioral problems. A post hoc analysis of combining the two instruments found this to be more effective than the individual instruments alone in identifying children referred to clinical services at 18 months. Further analysis at the level of single items is warranted to improve these screening instruments.

Interpregnancy interval and risk of autistic disorder.

BACKGROUND: A recent California study reported increased risk of autistic disorder in children conceived within a year after the birth of a sibling. METHODS: We assessed the association between interpregnancy interval and risk of autistic disorder using nationwide registry data on pairs of singleton full siblings born in Norway. We defined interpregnancy interval as the time from birth of the first-born child to conception of the second-born child in a sibship. The outcome of interest was autistic disorder in the second-born child. Analyses were restricted to sibships in which the second-born child was born in 1990-2004. Odds ratios (ORs) were estimated by fitting ordinary logistic models and logistic generalized additive models. RESULTS: The study sample included 223,476 singleton full-sibling pairs. In sibships with interpregnancy intervals <9 months, 0.25% of the second-born children had autistic disorder, compared with 0.13% in the reference category (≥ 36 months). For interpregnancy intervals shorter than 9 months, the adjusted OR of autistic disorder in the second-born child was 2.18 (95% confidence interval 1.42-3.26). The risk of autistic disorder in the second-born child was also increased for interpregnancy intervals of 9-11 months in the adjusted analysis (OR = 1.71 [95% CI = 1.07-2.64]). CONCLUSIONS: Consistent with a previous report from California, interpregnancy intervals shorter than 1 year were associated with increased risk of autistic disorder in the second-born child. A possible explanation is depletion of micronutrients in mothers with closely spaced pregnancies.

Early growth patterns in children with autism.

BACKGROUND: Case-control studies have found increased head growth during the first year of life in children with autism spectrum disorder. Length and weight have not been as extensively studied, and there are few studies of population-based samples. METHODS: The study was conducted in a sample of 106,082 children from the population-based Norwegian Mother and Child Cohort. The children were born in 1999-2009; by the end of follow-up on 31 December 2012, the age range was 3.6 through 13.1 years (mean 7.4 years). Measures were obtained prospectively until age 12 months for head circumference and 36 months for length and weight. We compared growth trajectories in autism spectrum disorder cases and noncases using Reed first-order models. RESULTS: Subjects included 376 children (310 boys and 66 girls) with specialist-confirmed autism spectrum disorder. In boys with autism spectrum disorder, mean head growth was similar to that of other boys, but variability was greater, and 8.7% had macrocephaly (head circumference > 97th cohort percentile) by 12 months of age. Autism spectrum disorder boys also had slightly increased body growth, with mean length 1.1 cm above and mean weight 300 g above the cohort mean for boys at age 12 months. Throughout the first year, the head circumference of girls with autism spectrum disorder was reduced-by 0.3 cm at birth and 0.5 cm at 12 months. Their mean length was similar to that of other girls, but their mean weight was 150-350 g below at all ages from birth to 3 years. The reductions in mean head circumference and weight in girls with autism spectrum disorder appear to be driven by those with intellectual disability, genetic disorders, and epilepsy. DISCUSSION: Growth trajectories in children with autism spectrum disorder diverge from those of other children and the differences are sex specific. Previous findings of increased mean head growth were not replicated.

Analysis of self-selection bias in a population-based cohort study of autism spectrum disorders.

BACKGROUND: This study examined potential self-selection bias in a large pregnancy cohort by comparing exposure-outcome associations from the cohort to similar associations obtained from nationwide registry data. The outcome under study was specialist-confirmed diagnosis of autism spectrum disorders (ASDs). METHODS: The cohort sample (n = 89 836) was derived from the population-based prospective Norwegian Mother and Child Cohort Study and its substudy of ASDs, the Autism Birth Cohort (ABC) study. The nationwide registry data were derived from the Medical Birth Registry of Norway (n = 507 856). The children were born in 1999­2007, and seven prenatal and perinatal exposures were selected for analyses. RESULTS: ASDs were reported for 234 (0.26%) children in the cohort and 2072 (0.41%) in the nationwide population. Compared with the nationwide population, the cohort had an under-representation of the youngest women (<25 years), those who had single status, mothers who smoked during pregnancy, and non-users of prenatal folic acid supplements. The ratios of the adjusted odds ratios (ORs) in the cohort over the adjusted ORs in the nationwide population were as follows; primipara pregnancy: 1.39/1.22, prenatal folic acid use: 0.85/0.86, prenatal smoking: 1.20/1.17, preterm birth (<37 weeks): 1.48/1.42, low birthweight (<2500 g): 1.60/1.58, male sex: 4.39/4.59 (unadjusted only); and caesarean section history: 1.03/1.04. CONCLUSIONS: Associations estimated between ASDs and perinatal and prenatal exposures in the cohort are close to those estimated in the nationwide population. Self-selection does not appear to compromise validity of exposure-outcome associations in the ABC study.

Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children.

IMPORTANCE: Prenatal folic acid supplements reduce the risk of neural tube defects in children, but it has not been determined whether they protect against other neurodevelopmental disorders. OBJECTIVE: To examine the association between maternal use of prenatal folic acid supplements and subsequent risk of autism spectrum disorders (ASDs) (autistic disorder, Asperger syndrome, pervasive developmental disorder-not otherwise specified [PDD-NOS]) in children. DESIGN, SETTING, AND PATIENTS: The study sample of 85,176 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study (MoBa). The children were born in 2002-2008; by the end of follow-up on March 31, 2012, the age range was 3.3 through 10.2 years (mean, 6.4 years). The exposure of primary interest was use of folic acid from 4 weeks before to 8 weeks after the start of pregnancy, defined as the first day of the last menstrual period before conception. Relative risks of ASDs were estimated by odds ratios (ORs) with 95% CIs in a logistic regression analysis. Analyses were adjusted for maternal education level, year of birth, and parity. MAIN OUTCOME MEASURE: Specialist-confirmed diagnosis of ASDs. RESULTS: At the end of follow-up, 270 children in the study sample had been diagnosed with ASDs: 114 with autistic disorder, 56 with Asperger syndrome, and 100 with PDD-NOS. In children whose mothers took folic acid, 0.10% (64/61,042) had autistic disorder, compared with 0.21% (50/24,134) in those unexposed to folic acid. The adjusted OR for autistic disorder in children of folic acid users was 0.61 (95% CI, 0.41-0.90). No association was found with Asperger syndrome or PDD-NOS, but power was limited. Similar analyses for prenatal fish oil supplements showed no such association with autistic disorder, even though fish oil use was associated with the same maternal characteristics as folic acid use. CONCLUSIONS AND RELEVANCE: Use of prenatal folic acid supplements around the time of conception was associated with a lower risk of autistic disorder in the MoBa cohort. Although these findings cannot establish causality, they do support prenatal folic acid supplementation.

Differences across counties in the registered prevalence of autism, ADHD, epilepsy and cerebral palsy in Norway.

BACKGROUND: In 2012, we published an overview of the prevalence of developmental disorders and neurological diseases in children in Norway, which was unknown at the time. In this article we will compare diagnostics and treatment across counties and institutions. MATERIAL AND METHOD: The prevalence across counties of autism spectrum disorders, ADHD, epilepsy and cerebral palsy in children aged 0-12 was estimated with the aid of data from the Norwegian Patient Register for the years 2008-11. RESULTS: In the age group 6-12 years, nationwide prevalence amounted to 0.6% for autism spectrum disorders, 2.0% for ADHD, 0.9% for epilepsy and 0.3% for cerebral palsy. In total, 5.0% of all twelve-year-olds were registered with one or more of these diagnoses. The prevalence of autism spectrum disorders and ADHD varied between the counties, from 0.3% to 1.5% for autism spectrum disorders and from 1.1% to 3.5% for ADHD. For epilepsy and cerebral palsy there was little variation between the counties. Diagnostics and treatment of these four conditions are spread over 29 somatic hospitals and 102 units for child and youth psychiatry. INTERPRETATION: The variations across counties in the prevalence of autism spectrum disorders and ADHD are most likely due to variations in diagnostic practices. We ask whether it is appropriate to spread the provision of treatment across such a high number of institutions.

Birth outcomes in women with eating disorders in the Norwegian Mother and Child cohort study (MoBa).

OBJECTIVE: We explored the impact of eating disorders on birth outcomes in the Norwegian Mother and Child Cohort Study. METHOD: Of 35,929 pregnant women, 35 reported broad anorexia nervosa (AN), 304 bulimia nervosa (BN), 1,812 binge eating disorder (BED), and 36 EDNOS-purging type (EDNOS-P) in the six months before or during pregnancy. The referent comprised 33,742 women with no eating disorder. RESULTS: Pre-pregnancy body mass index (BMI) was lower in AN and higher in BED than the referent. AN, BN, and BED mothers reported greater gestational weight gain, and smoking was elevated in all eating disorder groups. BED mothers had higher birth weight babies, lower risk of small for gestational age, and higher risk of large for gestational age and cesarean section than the referent. Pre-pregnancy BMI and gestational weight gain attenuated the effects. CONCLUSION: BED influences birth outcomes either directly or via higher maternal weight and gestational weight gain. The absence of differences in AN and EDNOS-P may reflect small numbers and lesser severity in population samples. Adequate gestational weight gain in AN may mitigate against adverse birth outcomes. Detecting eating disorders in pregnancy could identify modifiable factors (e.g., high gestational weight gain, binge eating, and smoking) that influence birth outcomes.

Maternal eating disorders influence sex ratio at birth.

We explored sex ratio at birth, defined as the proportion of male live births, in women with anorexia nervosa, bulimia nervosa, binge eating disorder, and eating disorders not otherwise specified-purging type (EDNOS-P) relative to a referent group in a large population-based sample of 38,340 pregnant women in Norway. Poisson regressions were adjusted for mother's age, pre-pregnancy BMI, lifetime smoking status, maternal education, income, marital status, gestational age, and parity. Lower proportions of male live births were observed in the anorexia and bulimia groups, while binge eating disorder and EDNOS-P were associated with a higher proportion of male births. These data suggest that maternal eating disorders may influence offspring sex and that the direction of effect may vary by eating disorder subtype. If confirmed, this finding could provide evidence in formulating hypotheses regarding the consequences of eating disorders and determinants of sex ratio at birth.

Maternal concentrations of human chorionic gonadotropin (hCG) and risk for cerebral palsy (CP) in the child. A case control study.

BACKGROUND: Intrauterine conditions may be important in the development of cerebral palsy in the child. The hormone, human chorionic gonadotropin (hCG), is synthesized in the placenta, and hCG plays an important role in placental angiogenesis and development. Thus, maternal hCG concentrations may be an indicator of placental function and thereby the intrauterine environment for the offspring. We studied the associations of maternal concentrations of hCG during pregnancy with cerebral palsy in the child. METHODS: We performed a case-control study nested within a cohort of 29,948 pregnancies in Norway during 1992-1994. Cases were all women within the cohort who gave birth to a singleton child with cerebral palsy diagnosed before five years of age (n = 63). Controls were a random sample of women with a singleton child without cerebral palsy (n = 182). RESULTS: The adjusted odds ratio (OR) for cerebral palsyin the child was 0.78 (95% CI: 0.55-1.10) per log-transformed unit of maternal hCG in the 1 st trimester, and the OR was 1.42 (95% CI: 0.94-2.16) in the 2nd trimester. Thus, women who did not have high hCG concentrations in the 1 st trimester and low hCG concentrations in the 2nd trimester, had increased risk for giving birth to a child with cerebral palsy. Adjustments were made for pregnancy week of serum sampling, maternal age and parity. CONCLUSIONS: The abnormal hCG concentrations in pregnancies with cerebral palsy in the offspring, could suggest placental factors as causes of cerebral palsy.

[Revisiting the Forsdahl-Barker hypothesis]. / Gjensyn med Forsdahl-Barker-hypotesen.

The hypothesis about the influence of the environment in early life for later health and development has been the basis for several hundred studies over the last two decades. Despite some diverging results in different studies and methodological shortcomings, including selection and confounding from socio-economic and other factors, there seems to be substantial evidence to the effect that the environment in early life is essential for later health and development. The association of low birthweight and risk of cardiovascular disease later in life is the most consistent finding, though the causal pathways for this connection have not been traced. Permanent damage caused by inadequate nutrition in critical periods of early life expressed as chronic disease later in life is a favoured hypothesis. To further elucidate potential mechanisms, there is a need for refining the measurement parameters for early experience. Placenta function, quality of nutrition, infections, hormonal and genetic factors may also play a role. The course-of-life approach claims that early life is an important period in human life, but not the only one. Continuous life events and socio-economic circumstances may modify early life experiences. Such an approach may be useful in order to see early life events in the right perspective.

Association of maternal report of infant and toddler gastrointestinal symptoms with autism: evidence from a prospective birth cohort.

IMPORTANCE: Gastrointestinal (GI) comorbidities are frequently described in association with autism spectrum disorder (ASD). However, the prevalence of GI disturbances and the age at which such problems first appear are unclear, and their specificity for ASD compared with other neurodevelopmental disorders is uncertain. OBJECTIVE: To compare maternal report of GI symptoms during the first 3 years of life in children with ASD, developmental delay (DD), and typical development (TD). DESIGN, SETTING, AND PARTICIPANTS: This large prospective cohort study consists of participants in the Norwegian Mother and Child Cohort Study. During a 10-year period (January 1, 1999, through December 31, 2008), women throughout Norway were recruited at the first prenatal ultrasonographic visit (approximately 18 weeks' gestation). The study enrolled 95,278 mothers, 75,248 fathers, and 114,516 children. Our analyses are based on MoBa data released through October 1, 2013, and NPR diagnoses registered through December 31, 2012, and include children born from January 1, 2002, through December 31, 2008, with completed age 18- and 36-month questionnaires. EXPOSURES: We defined 3 groups of children: children with ASD (n = 195), children with DD and delayed language and/or motor development (n = 4636), and children with TD (n = 40 ,95). MAIN OUTCOMES AND MEASURES: The GI symptoms were based on maternal report of constipation, diarrhea, and food allergy/intolerance. RESULTS: Children with ASD were at significantly increased odds of maternally reported constipation (adjusted odds ratio [aOR], 2.7; 95% CI, 1.9-3.8; P < .001) and food allergy/intolerance (aOR, 1.7; 95% CI, 1.1-2.6; P = .01) in the 6- to 18-month-old age period and diarrhea (aOR, 2.3; 95% CI, 1.5-3.6; P < .001), constipation (aOR, 1.6; 95% CI, 1.2-2.3; P < .01), and food allergy/intolerance (aOR, 2.0; 95% CI, 1.3-3.1; P < .01) in the 18- to 36-month-old age period compared with children with TD. Similar results for these symptom categories were observed in comparisons with children with DD, but ORs were slightly lower. Mothers of children with ASD were significantly more likely to report 1 or more GI symptom in either the 6- to 18-month or the 18- to 36-month-old age period and more than twice as likely to report at least 1 GI symptom in both age periods compared with mothers of children with TD or DD. CONCLUSIONS AND RELEVANCE: In this large prospective cohort, maternally reported GI symptoms are more common and more often persistent during the first 3 years of life in children with ASD than in children with TD or DD.

Sensorineural hearing loss in children: the association with Apgar score. A registry-based study of 392,371 children in Norway.

OBJECTIVES: The causes of congenital permanent hearing loss in children are insufficiently understood. We studied the association of Apgar score 5 min after birth with sensorineural hearing loss diagnosed before the age of 5 years. METHODS: We performed an epidemiological cohort study with data obtained by linkage between The Medical Birth Registry of Norway and the Norwegian County Registry of Children with Hearing Loss. Cases were 327 children born in Norway during the period 1978-1998 with sensorineural hearing loss. Controls were all children in Norway without sensorineural hearing loss born in the same counties and during the same period as the cases (n=392,044). The associations of Apgar score 5 min after birth with sensorineural hearing loss were estimated as odds ratios (OR) with 95% confidence intervals (CI) by applying logistic regression analyses. RESULTS: Among children with sensorineural hearing loss 0.9% (3/327) had Apgar score<3, whereas that was true for 0.1% (304/392044) of children without hearing loss (p=0.001, chi square test). The aOR for sensorineural hearing loss was 7.5 [95% CI 2.3-, 24.2] comparing Apgar score<3 to Apgar score 10, after adjustment for birthweight and concurrent birth defects. Most children with sensorineural hearing loss (90%) had Apgar score>8 five minutes after birth. CONCLUSIONS: Low Apgar score was associated with childhood sensorineural hearing loss. However, most children with sensorineural hearing loss, had Apgar score>8.

Parental obesity and risk of autism spectrum disorder.

OBJECTIVES: The objective of the study was to investigate the associations among maternal prepregnancy BMI, paternal BMI, and the risk of autism spectrum disorders (ASDs) in children. METHODS: The study sample of 92 909 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study. The age range was 4.0 through 13.1 (mean 7.4) years. Relative risks of ASDs were estimated by odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression models. RESULTS: At the end of follow-up on December 31, 2012, 419 children in the study sample had been diagnosed with ASDs: 162 with autistic disorder, 103 with Asperger disorder, and 154 with pervasive developmental disorder not otherwise specified. Maternal obesity (BMI ≥30) was only weakly associated with ASD risk, whereas paternal obesity was associated with an increased risk of autistic disorder and Asperger disorder. The risk of autistic disorder was 0.27% (25 of 9267) in children of obese fathers and 0.14% (59 of 41 603) in children of fathers with normal weight (BMI <25), generating an adjusted OR of 1.73 (95% CI: 1.07-2.82). For Asperger disorder, analyses were limited to children aged ≥7 years (n = 50 116). The risk was 0.38% (18 of 4761) in children of obese fathers and 0.18% (42 of 22 736) in children of normal-weight fathers, and the adjusted OR was 2.01 (95% CI: 1.13-3.57). No associations were found for pervasive developmental disorder not otherwise specified. CONCLUSIONS: Paternal obesity is an independent risk factor for ASDs in children. The associations should be investigated further in genetic and epigenetic studies.

Autism spectrum disorder, ADHD, epilepsy, and cerebral palsy in Norwegian children.

BACKGROUND: Numerous studies have investigated the prevalence of neurologic and neurodevelopmental disorders individually, but few have examined them collectively, and there is uncertainty as to what extent they overlap. METHODS: The study has determined the proportions of children aged 0 to 11 years with diagnoses of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), epilepsy, and cerebral palsy (CP) in Norway. The data were obtained from the Norwegian Patient Register, which is nationwide and contains diagnoses assigned by Norwegian specialist health services (hospitals and outpatient clinics). The Norwegian Patient Register started collecting individual-level data in 2008, and the follow-up period for the study is years 2008 through 2010. RESULTS: For ASD, ADHD, and epilepsy, the proportions were highest in the oldest children. At age 11 years, the incidence was 0.7% for ASD, 2.9% for ADHD, and 0.9% for epilepsy. The cumulative incidence is likely to be higher because some cases diagnosed before 2008 were probably missed. For CP, the proportions were ~0.3% for age ≥ 5 years. There was considerable overlap between diagnoses. For all disorders, boys had a significantly increased risk. In school-age children (aged 6-11 years) the male/female ratio was 4.3 for ASD, 2.9 for ADHD, 1.2 for epilepsy, and 1.3 for CP. CONCLUSIONS: The findings demonstrate the significant burden of disease associated with neurologic and neurodevelopmental disorders in children and that this burden is disproportionately skewed toward boys.

Association of cerebral palsy with Apgar score in low and normal birthweight infants: population based cohort study.

OBJECTIVES: To assess the association of Apgar score 5 minutes after birth with cerebral palsy in both normal weight and low birthweight children, and also the association with the cerebral palsy subdiagnoses of quadriplegia, diplegia, and hemiplegia. DESIGN: Population based cohort study. SETTING: The Medical Birth Registry of Norway was used to identify all babies born between 1986 and 1995. These data were linked to the Norwegian Registry of Cerebral Palsy in Children born 1986-95, which was established on the basis of discharge diagnoses at all paediatric departments in Norway. POPULATION: All singletons without malformations born in Norway during 1986-95 and who survived the first year of life (n=543 064). MAIN OUTCOME MEASURE: Cerebral palsy diagnosed before the age of 5 years. RESULTS: 988 children (1.8 in 1000) were diagnosed with cerebral palsy before the age of 5 years. In total, 11% (39/369) of the children with Apgar score of less than 3 at birth were diagnosed with cerebral palsy, compared with only 0.1% (162/179 515) of the children with Apgar score of 10 (odds ratio (OR) 53, 95% CI 35 to 80 after adjustment for birth weight). In children with a birth weight of 2500 g or more, those with an Apgar score of less than 4 were much more likely to have cerebral palsy than those who had an Apgar score of more than 8 (OR 125, 95% confidence interval 91 to 170). The corresponding OR in children weighing less than 1500 g was 5 (95% CI 2 to 9). Among children with Apgar score of less than 4, 10-17% in all birthweight groups developed cerebral palsy. Low Apgar score was strongly associated with each of the three subgroups of spastic cerebral palsy, although the association was strongest for quadriplegia (adjusted OR 137 for Apgar score <4 v Apgar score >8, 95% CI 77 to 244). CONCLUSIONS: Low Apgar score was strongly associated with cerebral palsy. This association was high in children with normal birth weight and modest in children with low birth weight. The strength of the association differed between subgroups of spastic cerebral palsy. Given that Apgar score is a measure of vitality shortly after birth, our findings suggest that the causes of cerebral palsy are closely linked to factors that reduce infant vitality.