Sex differences in early vulnerability to cerebral injury and their neurodevelopmental implications

Abstract

Sex differences in early vulnerability to cerebral injury were examined in a lO-year cohort of preterm infants. The 173 infants, whose gestational age was 32 weeks or less, were diagnosed with intracranial hemorrhage (lCH), the most common cerebral insult in the premature neonate. Determination of ICH severity was based on neuroimaging evidence obtained during the neonatal period. Because the females in the sample exhibited greater dysmaturity coupled with lower birthweight, as compared with their male counterparts, analysis of covariance was applied to the data After statistically controlling for the influence of potentially confounding perinatal variables, gender was found to provide a unique contribution to extent of ventricular dilation, an index of ICH severity. Male sex was associated not only with greater ventriculomegaly, but also with a higher grade of ICH. The latter effect was demonstrable in a large subsample of 72 males and 77 females whose birthweights were 1,750 g or below, and who did not differ significantly in gestational age. The implications of these results for theories about the neurobiological origins of sex differences in susceptibility to deviation from normal development are addressed.Beginning with gestation, the human male is more vulnerable to adversity than the human female. There is a higher frequency of miscarried and stillborn males (Baumgartner, Pessin, Wegman,

Severity of perinatal cerebral injury and developmental outcome: A dose-response relationship.

“…Our findings seem to be consistent with the differential maturation hypothesis (Geschwind & Galaburda, 1985; Taylor, 1969). Given heightened left hemisphere vulnerability—a result of the putative lag in left hemisphere maturation (Raz et al, 1994)—one would predict a stronger association between perinatal left, rather than right, hemispheric lesions and subsequent acquisition of intellectual function. The results suggest, however, that the severity of the lesion suffered by the left hemisphere is a more potent predictor not only of verbal performance—a function of the left hemisphere—but also of visuospatial performance—a function mediated primarily by the right hemisphere.…”

“…The concurrent validity of the radiological rankings was established by studying their relationships with a continuous computer-based planimetric measure of ventricular size. These findings are reported elsewhere (see Raz, Goldstein, et al, 1994). Briefly, the scans of 18 infants were obtained prospectively.…”

“…Although quite respectable, this ICC is probably an underestimate of the true inter-rater reliability for severity diagnoses, because it reflects both inter-rater agreement and stability across time. The reliability estimates of the radiological determinations of uni-vs. bilaterality of ICH are reported in Raz, Foster, et al(1994).…”

“…In addition, the groups were similar in age, socioeconomic status, parents' education, and mother's IQ. Seventeen children from this sample had previously been included in a study on the relationship between lesion side and cognitive asymmetry (Raz, Foster, Briggs, et al, 1994), and all participated in a study on sex differences in cognitive performance (Raz, Lauterbach, et al, 1994).…”

“…The inter-rater reliability of the ventriculomegaly rankings is reported elsewhere (see Raz, Goldstein, et al, 1994). Briefly, the intraclass correlation coefficient (ICC; Shrout & Fleiss, 1979) was determined for two experienced neuroradiologists.…”