Extreme prematurity in healthy 5-year-old children: A re-analysis of sex effects on event-related brain activity MARC E. LAVOIE, a PHILIPPE ROBAEY, a JOHANNES E.A. STAUDER, b JACQUELINE GLORIEUX, c and FRANCINE LEFEBVRE c a Cognitive Psychophysiology and Neuropsychiatry Laboratory, Department of Psychiatry, Sainte-Justine Hospital, University of Montréal, Québec, Canada b Research Unit, Rivière-des-Prairies Hospital, Cognitive Psychophysiology Laboratory, Department of Psychology, University of Montréal, Québec, Canada c Department of Pediatric, Service of Neonatology, Sainte-Justine Hospital, University of Montréal, Québec, Canada Abstract A male disadvantage has been reported in several outcome studies of children born preterm. Twenty-two healthy premature children ~10 girls, 12 boys! born between 25 and 28 weeks of gestation and 20 controls born full-term ~10 boys, 10 girls! were matched on socioeconomical status and age. Event-related potentials ~ ERPs! were recorded by using 14 electrodes in a visual oddball task, with 75% frequent and 25% rare stimuli. This task elicited a larger P3 to the rare than to the frequent stimuli, with a prominent parietocentral localization. However, the amplitude was larger in full-term boys than in full-term girls, a difference that was not observed between preterm boys and preterm girls, especially to targets and on the central electrodes. In addition, the preterm group was characterized by a frontal slow wave larger in boys than in girls. In these prematures, the lack of the sex-related difference may be accounted by differences in the strength of the neuronal generators in males, as they might have been affected by the high level of androgens by the fetal testis under the control of placental gonadotropes during the first two thirds of gestation. Descriptors: Prematurity, Sex, Event-related potentials, Oddball effect Within the past two decades, the cognitive development of preterm children and the different pathways between premature boys and girls have been the focus of various studies in developmental psy- chology and pediatrics. In the 1980s, it was reported frequently that premature boys had a significantly higher mortality rate and more postnatal complications than premature girls ~ Resnick et al., 1989; Yu et al., 1986!. However, equal neonatal mortality has been more recently reported ~ Verloove-Vanhorick et al., 1994!. For pre- term male survivors, long-term neurodevelopmental sequelae are also more apparent ~ Hoffman & Bennett, 1990!. At 2 years of age, preterm males demonstrated lower skills in language and social communication than preterm females, and twice as many boys as girls showed major neurodevelopmental problems ~ Brothwood, Wolke, Gamsu, Benson, & Cooper, 1986; Hirata et al., 1983!. Among 1,007 premature children of 32 weeks of gestation or less ~ Verloove-Vanhorick et al., 1994!, the prevalence of handicap, defined as a role limitation in everyday life, was three times higher in boys than in girls ~21% vs. 7%!. Adjustment for gestational age, birth weight, or perinatal variables did not change this odds ratio. As the male disadvantage was not related to lower mortality, and permeated all assessed areas, sex appeared as an important deter- minant of handicap. Because handicaps result from brain impair- ment and neuropsychological disabilities, this male disadvantage could be due to sex-related differences in health complications observed at birth, in particular in hypoxic-ischemic brain insult. Hypoxia-ischemia is triggered by the frequent respiratory prob- lems that occur in preterm infants and is the prominent factor in the complex etiology of the most common brain insult in the preterm infant, intracranial hemorrhage. Within this perspective, Raz et al. ~1995! addressed the specific issue of an outcome difference be- tween boys and girls following perinatal intracranial hemorrhage. In a cohort of 173 preterm children ~37 weeks of gestation or less! followed over 3 years, these authors also observed sex-related differences in cognitive outcome. Girls were similar to boys re- garding sociofamilial background and antepartum, intrapartum, and This article was written in partial fulfillment of the requirements for a doctoral degree at the University of Montreal. We gratefully acknowledge the support of the Fonds de la Recherche en Santé du Québec ~ FRSQ! and the Conseil Québecois de la Recherche Sociale ~CQRS!. This work was supported by a Ph.D. fellowship ~ FRSQ! to M.E. Lavoie and a clinician- scientist awards ~ FRSQ! to P. Robaey. Special thanks go to Anne Bolduc for evaluation and psychometric testing, Jocelyne Vallée for the recruitment of the subjects, Phetsamone Vannasing, Isabelle Lamothe, and Cecile Ladouceur for their highly com- petent technical assistance during recordings, and Maurits van der Molen for comments on an earlier version of this manuscript. We also express our gratitude to the patients and families who participated in the study. Address reprint requests to: Philippe Robaey, Centre de recherche de l’Hôpital Ste-Justine, Laboratoire de Psychophysiologie Cognitive et de Neuropsychiatrie, Département de Psychiatrie, Hôpital Sainte-Justine, 3100 Ellendale, Montréal, Québec, Canada H3S 1W3. E-mail: robaey@ere. umontreal.ca. Psychophysiology, 35 ~1998!, 679–689. Cambridge University Press. Printed in the USA. Copyright © 1998 Society for Psychophysiological Research 679