Rothman, Kenneth J.
Boston University Medical Center, 715 Albany Street, Boston, MA 02118.
In this issue of Epidemiology, Kieler and colleagues report that men who were exposed to ultrasound in utero appear to have a higher probability of becoming left-handed. 1 This curious finding raises several important questions. Is the finding real? Is it important? What should be done about it?
The study assesses ultrasound exposure from aggregate data. The University Hospital in Malmö was the first medical center in Sweden to use ultrasound scans as part of standard antenatal care. Males born at this medical center after the routine use of ultrasound was introduced were compared with males born during the same time period at other Swedish medical centers that had not yet introduced ultrasound. The study included only males because handedness was determined as part of eligibility testing for military service. There is no doubt that the rough method of assigning ultrasound exposure has misclassified some of the people in the study. To what extent could such misclassification of ultrasound exposure be related to the handedness of the offspring?
Low birth weight is related to handedness. It is theoretically possible that women in Malmö, the site of the exposed cohort, deliver a greater proportion of their babies with a low birth weight. Kieler et al had information available on birth weight, however, and found that controlling for differences in birth weight had little effect on the estimates in their study. Nor does any other selection or confounding factor appear to explain the admittedly modest association in their data between ultrasound and handedness. If anything, the possibilities for nondifferential misclassification seem greater than those for differential misclassification, which implies that the relation between ultrasound and handedness may be larger than what is reported.
Even if there is no obvious non-causal explanation for the finding, its novelty will certainly fuel skepticism. But let us suppose for a moment that this finding eventually is confirmed in other studies, and that it reflects a newly discovered causal relation. What would be its import? The estimated effect is about a 30% increase in the “risk” of being left-handed, which corresponds to an extra three left-handers among one hundred births. This effect in itself hardly constitutes a public-health problem. If this effect is causal, however, it raises the worrisome possibility that ultrasound exposure is also affecting the central nervous system in other ways that are less evident. An effect on the brain of three offspring in every one hundred would be a huge population effect, a potentially important public-health problem that could not be dismissed out-of-hand.
I do not mean to imply that we are damaging the brains of our unborn with ultrasound scans; for starters, no one knows yet whether the sinistrality finding will be borne out. Nevertheless, the possibility, however remote, of iatrogenic effects on the central nervous system is a prospect that merits serious attention. If confirmed, it would call for weighing potential adverse effects against the gains that ultrasound scanning provide. Unlike the generation of electromagnetic fields from power transmission lines or the contamination of air and drinking water by our industrial society, ultrasound is a deliberate exposure under each mother’s direct control. Nevertheless, its nearly ubiquitous application in western medicine underscores the importance of addressing this issue without delay, if for no other reason than to refute it promptly if it is a false alarm.
Unlike some other iatrogenic effects, such as vaginal cancer caused by diethylstilbestrol, an effect of ultrasound on handedness would elude the most astute clinician. If the effect is real, it will be a tribute to epidemiologic research. If it is wrong, it will provide further ammunition to the critics of epidemiology, who will scorn this finding as another example of the fluke observations that we epidemiologists seize upon as we allegedly torment society. So far no harm has been demonstrated. We should work quickly to avoid a needless scare, but we do need to test this finding and if possible set the matter to rest quickly one way or the other.
1. Kieler H, Cnattingius S, Haglund B, Palmgren J, Axelsson O. Sinistrality—a side-effect of prenatal sonography: a comparative study of young men. Epidemiology 2001; 12: 618–623.
© 2001 Lippincott Williams & Wilkins, Inc.