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.