Fetal growth restriction is not associated with a reduced risk for bilateral spastic cerebral palsy in very-low-birthweight infants

Objective: To evaluate the influence of confounding and sampling bias on th e relationship between fetal growth restriction in a very-low-birthweight-d efined cohort (VLBW, less than or equal to 1500 g) and bilateral spastic ce rebral palsy (BSCP) at early school-age. Methods: Three hundred twenty-four of 407 long-term survivors of a regional cohort of VLBW newborns were foll owed until age 6 years. We categorized as small for gestational age (SGA) a ll infants whose birthweight Z-score was below -2 relative to published ref erence values. Uni- and multivariable logistic regression models were fit t o estimate the risk of BSCP associated with SGA in the total sample, in sub samples defined by gestational age, and in a gestational age-matched case-c ontrol sample. Results: In the total sample, no child below 28 wet ks was S GA, and no child above 32 weeks had an appropriate birthweight for gestatio nal age (AGA). The prevalence of BSCP was 14% in AGA and 2% in SGA infants. In both uni- sind multivariable logistic regression analyses of the total sample, SGA was associated with a prominently reduced risk of BSCP (odds ra tios range from 0.1 to 0.2, all 95% confidence limits exclude 1.0). However , analyses performed in samples defined by different gestational age cutoff s (24-31 weeks, 28-31 weeks) and in a sample using three gestational age-ma tched controls per BSCP-case did not show a protection by growth restrictio n (odds ratios range from 0.8 to 2.2, all 95% confidence limits include 1.0 ). Conclusions: In VLBW-defined samples, the apparent protective effect of SGA for BSCP can be explained, at least in part, by the highly skewed distr ibution of SGA over the available gestational age range. From this follows that study cohorts should be defined by gestational age and not by birthwei ght. In distorted samples like this one, even controlling for gestational a ge does not reduce the illusion of a reduced cerebral palsy risk for growth restricted infants. Only restriction of the sample by gestational age and/ or matching for gestational age reveals the absence of this apparent protec tive effect. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.