On a possible early identification procedure for babies at high risk for autistic spectrum disorder

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Summary

A hypothesis for a method that may make possible the early identification of neonates at high risk for later development of autistic spectrum disorder (ASD) is set forth. The method is a test of the assertion that unusually high testosterone concentrations in amniotic fluid (TECAFs) are predictive of later ASD diagnoses. The statistical distribution of TECAFS, obtained in the 14–20th week of pregnancy, is used to determine the critical TECAF value above which the highest 2% lie and thus identify the babies at high risk for later ASD syndromes. From presently available data a single numerical value cannot be obtained. However, a critical value calculated from the mean TECAF value of a group of gender identified amniotic fluid samples, which are all assayed by the same technique, and multiples of the standard deviation (SD) of the TECAFs of that group, leads to an estimate of the critical TECAF value. We estimate that this critical value is equal to the mean plus 2.6 times the standard deviation, (m + 2.6 SD), of the set of measurements. A rough calculation of the number of neonates that would be needed for a test of this method is discussed.

Introduction

This paper explores a procedure that may make possible the neonatal identification of babies who may be at high risk for possible later diagnosis of an autistic spectrum disorder (ASD) in the first few years of their lives [1], [2].

Refs. [3], [4], [5] are among several studies touching upon the likelihood that a high Testosterone Concentration in the Amniotic Fluid (TECAF) of a fetus may be an important factor in the gestation of a child who later exhibits ASD. However, we know of no studies establishing a definite link between an ASD diagnosis and earlier measurements of testosterone concentration in amniotic fluid. In particular, the TECAF during the 14–20th weeks of pregnancy would be a convenient benchmark since a large fraction of amniotic fluid withdrawals are conducted in approximately those weeks of pregnancy. Estimates of the frequency of ASD, commonly identified in US born children by approximately 48 months of age, most recently range as high as 0.6% (1 in 166 of all births) [6]. The ratio of male to female ASD occurrences is known to be about 4:1; thus, about 1% of male babies (1 in 104 births), and about 0.2% of female babies (1 in 415 births) born during the current year can be projected to exhibit one or more characteristics of ASD within the first several years of their lives.

Section snippets

Hypothesis and pertinent background

With this brief introduction, we now set forth our hypothesis for a possible early high risk identification of ASD procedure (EHRIA). Specifically, we propose to test the validity of the proposition that unusually high TECAFs are predictive of later ASD diagnoses. The next paragraphs outline the reasoning upon which verification of the proposed EHRIA procedure is based.

If a large number of TECAF measurements – at least 100, preferably 300 or more – obtained from fetuses previously identified as

Empirical data and interpretation

The literature includes numerous papers setting forth measurements of TECAFs. We have found only a few of these [7], [8] that include single sex samples greater than 100. The majority of the papers were published fifteen or more years ago, frequently investigating the possibilities of TECAF as a method of establishing a fetus’s gender. Almost all include mean values and their SDs; none tabulate individual TECAF values. Several papers provide some form of graphic presentation, from which,

Results

The spread of TECAF data found in the literature – even if only the data using the RIA with chromatography technique is considered – is such that it is not possible from that data to arrive at a numerical value of TECAF above which a high risk of later ASD symptoms may exist. Until considerably more and better categorized data is accumulated, the TECAF value expressed as a [mean + multiple of SD] value can be exploited to test the correlation between very high TECAF measurements and later high

Discussion

It must be emphasized immediately that the “high risk” designation defined above is based on statistical analysis, and cannot be interpreted as a definitive evaluation or decision about the future health status of the particular source of a TECAF sample.

A first guess of patients able and willing to participate in a longitudinal data gathering and tracking cycle such as is here proposed to test the validity of the EHRIA procedure is optimistically suggested to be around two-thirds of the 840

Acknowledgements

We are indebted to Ms. Sandra Martin, Assistant Director, Shifman Medical Library, Wayne State University for valuable assistance in the identification and assembly of reference literature. Clarifications about TECAF assay techniques by Dr. Marappa Subramanian, Director of Operations at the Wayne State University Mott Center for Human Growth and Development, were very helpful. We wish to thank Professors L. Favro and P. Keyes, our Physics Department colleagues, for several discussions about the

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