Pregnancy and Birth Complications in Autism and Liability to the Broader Autism Phenotype

doi:10.1097/00004583-200205000-00015

Journal of the American Academy of Child & Adolescent Psychiatry

Volume 41, Issue 5, May 2002, Pages 572-579

https://doi.org/10.1097/00004583-200205000-00015 Get rights and content

ABSTRACT

Objective

To understand better the relationship between pregnancy and birth complications and genetic factors in autism.

Method

The sample included 78 children with an autism spectrum disorder and 88 unaffected siblings. A standardized interview was used to ask mothers about the pregnancy and birth of each child, and an overall index reflecting freedom from complications (termed “optimality”) was determined. The presence of autism-like traits (termed the “broader autism phenotype”) in second- and third-degree relatives was ascertained by reports from multiple informants. The proportion of relatives with the broader autism phenotype, corrected for degree of relation, was used as an index of family loading.

Results

Children with autism spectrum disorders have lower optimality (higher rates of complications) than unaffected siblings. High family loading for the broader autism phenotype is associated with higher rates of complications in unaffected siblings. Family loading was not significantly associated with complications in affected siblings in this sample. Overall, these findings argue against complications being a direct cause of autism, as one would expect to find the most complications in sporadic cases (i.e., in children without a positive family history).

Conclusion

Increased rates of birth and pregnancy complications are likely secondary to familial factors associated with autism.

Section snippets

Sample

The sample for this study consists of a series of families with at least one child who is affected with an autism spectrum disorder. Families with two or more affected children (multiplex) were recruited systematically across the province of Ontario (for full details, see Mahoney et al., 1998), and families with one affected child were taken from a consecutively referred clinic sample. For inclusion, families were required to include at least one unaffected sibling, so that analyses involving

Sample

Excluding those multiplex families with no unaffected siblings for comparison, there was a total of 60 families, including 78 affected and 88 unaffected children (whose characteristics are summarized in Table 1). Family loading data were available for 43 families (including 55 affected and 68 unaffected); the remaining families were excluded from analyses involving this variable. There were a total of 444 second-degree relatives and 514 third-degree relatives. There were an additional 43

DISCUSSION

This report contributes to evidence for an association between obstetric optimality and autism spectrum disorder, and it tests contrasting hypotheses regarding potential mechanisms. The main findings are that (1) individuals with PDD had lower obstetric optimality (greater adversity during pregnancy and birth) than did their unaffected siblings, even after we controlled for birth order; (2) family loading for the broader autism phenotype was associated with optimality in unaffected siblings of

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Meanwhile, some simple adaptive practices are possible, such as, after a caesarean section, wrapping the neonate in clothes recently worn by the mother and, occasionally, putting the neonate in the arms of a person who is cohabiting with the mother.
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Registry-based case-control study from all singleton births in Finland from 1990-2005. Cases with childhood autism, Asperger syndrome, or PDD (n = 4713) were identified from the Finnish Hospital Discharge Register. Each case was matched to 4 controls on sex, date of birth, and place of birth. Information on obstetric risk factors was from the Finnish Medical Birth Register. Conditional logistic regression models were used for statistical analyses.
When adjusted with confounders, childhood autism was associated with maternal high blood pressure (OR 1.49, 95% CI 1.1-2.1, P = .018), Apgar scores less than 7 (1 minute, OR 1.46, 95% CI 1.1-2.0, P = .021), and neonatal treatment with monitoring (OR 1.40, 95% CI 1.02-1.9, P = .038). PDD was associated with induced labor (OR 1.25 95% CI 1.1-1.5, P = .007), planned cesarean delivery (OR 1.34, 95% CI 1.1-1.7, P = .009), 1-minute Apgar scores 7-8 ( OR 1.22, 95% CI 1.1-1.4, P = .008) and less than 7 (OR 1.34, 95% CI 1.03-1.8, P = .032), and neonatal intensive care unit treatment (OR 1.52, 95% CI 1.2-2.0, P = .003). Asperger syndrome was associated only with 1-minute Apgar scores 7-8 (OR 1.19, 95% CI 1.03-1.4, P = .018).
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Incidence of Autism Spectrum Disorder (ASD) is increasing across the globe and no data is available from India regarding the risk factors of ASD. In this regard a questionnaire based epidemiological assessment was carried out on prenatal, perinatal and neonatal risk factors of ASD across 8 cities in India. A retrospective cohort of 942 children was enrolled for the study. 471 children with ASD, under age of 10, were analyzed for pre-, peri-, and neonatal factors and were compared with the observations from equal number of controls. The quality control of the questionnaire and data collection was done thoroughly and the observations were computed statistically. A total of 25 factors were evaluated by unadjusted and adjusted analysis in this study. Among the prenatal factors considered, advanced maternal age, fetal distress and gestational respiratory infections were found to be associated with ASD and had an odds ratio of 1.8. Evaluation of perinatal and neonatal risk factors showed labor complications, pre-term birth, neonatal jaundice, delayed birth cry and birth asphyxia to be associated with ASD with an odds ratio greater than 1.5. This important study, first of its kind in Indian population gives a firsthand account of the relation of pre-, peri- and neonatal risk factors on ASD from an ethnically and socially diverse country like India, the impact of which was unknown earlier. This advocates additional focused investigations on physiological and genetic changes contributed by these risk factor inducing environments.
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Although significant genetic links have been found, with evidence from monozygotic twin and family studies showing concordance rates for ASDs at least up to 60 percent and a familial risk 5–10 times higher than that for the general population (Bailey et al., 1995; Rutter, 2000; Szatmari, 1999), the underlying etiology of ASDs is still unknown. Many different theories researching the biological basis of ASDs have been suggested, including multiple genetic mutation, chromosomal abnormalities, epiphenomena (pre- and peri-natal complications interact with genetic factors), and immune hypotheses (Ashwood & Van de Water, 2004; Brimacombe, Ming, & Lamendola, 2007; Kolevzon, Gross, & Reichenberg, 2007; Newschaffer, Fallin, & Lee, 2002; Santangelo & Tsatsanis, 2005; Zwaigenbaum et al., 2002). Similar to the substantially increased prevalence of ASDs worldwide over the last few decades, the prevalence rates of asthma, allergic rhinitis (AR), and atopic dermatitis (AD) have risen gradually and simultaneously.
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: At the time of this work, Dr. Zwaigenbaum was supported by a Duncan L. Gordon Fellowship from the Hospital for Sick Children Foundation and a New Investigator Fellowship from the Ontario Mental Health Foundation. This work is supported by grant 11350 from the Medical Research Council of Canada.

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ARTICLESPregnancy and Birth Complications in Autism and Liability to the Broader Autism Phenotype

ABSTRACT

Objective

Method

Results

Conclusion

Section snippets

Sample

Sample

DISCUSSION

J Am Acad Child Adolesc Psychiatry

J Am Acad Child Adolesc Psychiatry

J Am Acad Child Adolesc Psychiatry

J Am Acad Child Adolesc Psychiatry

Am J Hum Genet

Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)

Autism as a strongly genetic disorder: evidence from a British twin study

Psychol Med

Autism: the phenotype in relatives

J Autism Dev Disord

Chromosomal abnormalities

A case-control family history study of autism

J Child Psychol Psychiatry

Autism and developmental abnormalities in children with perinatal cocaine exposure

J Natl Med Assoc

Pregnancy, delivery and neonatal complications among autistic children

Am J Dis Child

Infantile autism: a genetic study of 21 twin pairs

J Child Psychol Psychiatry

Infantile autism: a total population study of reduced optimality in the pre-, peri-, and neonatal periods

J Autism Dev Disord

Stoppage rules and genetic studies of autism

J Autism Dev Disord

Prenatal, perinatal, and neonatal factors in autism, pervasive developmental disorder-not otherwise specified, and the general population

Pediatrics

A broader phenotype of autism: the clinical spectrum in twins

J Child Psychol Psychiatry

Leiter International Performance Scale: A Handbook (Arthur Adaptation)

A comparison of obstetrical records of autistic and nonautistic referrals for psychoeducational evaluations

J Autism Dev Disord

ARTICLES
Pregnancy and Birth Complications in Autism and Liability to the Broader Autism Phenotype