The recurrence risk of autism spectrum disorders (ASD) is estimated to be between 3% and 10%, but previous research was limited by small sample sizes and biases related to ascertainment, reporting, and stoppage factors. This study used prospective methods to obtain an updated estimate of sibling recurrence risk for ASD.
A prospective longitudinal study of infants at risk for ASD was conducted by a multisite international network, the Baby Siblings Research Consortium. Infants (n = 664) with an older biological sibling with ASD were followed from early in life to 36 months, when they were classified as having or not having ASD. An ASD classification required surpassing the cutoff of the Autism Diagnostic Observation Schedule and receiving a clinical diagnosis from an expert clinician.
A total of 18.7% of the infants developed ASD. Infant gender and the presence of >1 older affected sibling were significant predictors of ASD outcome, and there was an almost threefold increase in risk for male subjects and an additional twofold increase in risk if there was >1 older affected sibling. The age of the infant at study enrollment, the gender and functioning level of the infant's older sibling, and other demographic factors did not predict ASD outcome.
The sibling recurrence rate of ASD is higher than suggested by previous estimates. The size of the current sample and prospective nature of data collection minimized many limitations of previous studies of sibling recurrence. Clinical implications, including genetic counseling, are discussed.
Comments
What other characteristics do these baby sibs have in common?
The many causes of autism (genetic and non-genetic) will not be understood until the brain impairment underlying the specific language disorder of children with autism is discovered. Children with autism learn to speak using phrase fragments, which they often employ badly out of context. Why? Normal children do not learn language in this way, but begin to speak one syllable at a time, then use these syllables in patterns of "baby talk" or "telegraphic speech" consisting of words and word sequences of the child's own making to fit new contexts [1].
Consideration must be given to the possibility that auditory processing of speech sounds is impaired in children with autism. Rapin suggested that some children with autism suffer from "verbal auditory agnosia" [2].
What could be the cause of such early auditory agnosia? Kety (1962) demonstrated that blood flow in nuclei of the brainstem auditory pathway is greater than anywhere else in the brain [3]. Aerobic metabolism is also higher in the auditory system than other areas of the brain [4]. The auditory system is thus more susceptible to injury from toxic substances, like alcohol, valproic acid, and thalidomide, which have been identified as etiologic factors in some cases of autism. The auditory system is also more vulnerable to oxygen insufficiency at birth [5].
Consider present day protocols used in obstetrics. The rise in autism prevalence coincides with the practice begun in the mid 1980s of clamping the umbilical cord immediately at birth. What's wrong with this? Oxygen delivery from the mother does not cease immediately at birth. Blood flow from the placenta continues after birth, often for many minutes, unless abruptly terminated by clamping the umbilical cord. Older (and long forgotten) research studies provided ample evidence of this [6, 7].
The time required for transfer of respiration from placenta to the lungs may be a hereditary factor, and how hereditary factors of this kind may result in familial autism should be investigated. Males, with higher metabolic needs than females, are also more vulnerable to oxygen insufficiency at birth [8].
In addition to a diagnosis of autism, what other characteristics do these 132 baby sibs have in common? What prenatal exposures, difficulties at birth, need for cesarean delivery, or neonatal jaundice were recorded?
References
[1] Brown R. A First Language: The Early Stages. Cambridge, MA: Harvard University Press, 1973.
[2] Rapin I Autism. N Engl J Med. 1997 Jul 10;337(2):97-104.
[3] Kety SS. Regional neurochemistry and its application to brain function. Bull N Y Acad Med. 1962 Dec;38:799-812. Online at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1804882/?tool=pubmed
[4] Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M. The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem. 1977 May;28(5):897-916.
[5] Windle WF. Brain damage by asphyxia at birth. Sci Am. 1969 Oct;221(4):76-84.
[6] Gunther M. The transfer of blood between baby and placenta in the minutes after birth. Lancet. 1957 Jun 22;272(6982):1277-80.
[7] Stembera ZK, Hodr J, Janda J. Umbilical blood flow in healthy newborn infants during the first minutes after birth. Am J Obstet Gynecol. 1965 Feb 15;91:568-74.
[8] Simon N, Volicer L (1976) Neonatal asphyxia in the rat: greater vulnerability of males and persistent effects on brain monoamine synthesis. J Neurochem. 1976 May;26(5):893-900.
Conflict of Interest:
Mother of a son with autism