Fetal growth restriction and risk of cerebral palsy in singletons born after at least 35 weeks' gestation

Abstract

Objective: The objective of the study was to improve the understanding of etiological paths to cerebral palsy (CP) that include fetal growth restriction by examining factors associated with growth restriction that modify CP risk.

Study design: In a total population of singletons born at or after 35 weeks, there were 493 children with CP and 508 matched controls for whom appropriateness of fetal growth could be estimated. Fetal growth was considered markedly restricted if birthweight was more than 2 SD below optimal for gender, gestation, maternal height, and parity. We examined maternal blood pressure in pregnancy, smoking, birth asphyxia, and major birth defects recognized by age 6 years as potential modifiers of CP risk in growth-restricted births.

Results: More than 80% of term and late preterm markedly growth-restricted singletons were born following a normotensive pregnancy and were at statistically significantly increased risk of CP (odds ratio, 4.81; 95% confidence interval, 2.7-8.5), whereas growth-restricted births following a hypertensive pregnancy were not. Neither a clinical diagnosis of birth asphyxia nor potentially asphyxiating birth events occurred more frequently among growth-restricted than among appropriately grown infants with CP. Major birth defects, particularly cerebral defects, occurred in an increasing proportion of CP with increasing growth deficit. The factor most predictive of CP in growth-restricted singletons was a major birth defect, present in 53% of markedly growth-restricted neonates with later CP. Defects observed in CP were similar whether growth restricted or not, except for an excess of isolated congenital microcephaly in those born growth restricted. The highest observed CP risk was in infants with both growth restriction and a major birth defect (8.9% of total CP in this gestational age group, 0.4% of controls: odds ratio, 30.9; 95% confidence interval, 7.0-136).

Conclusion: The risk of CP was increased in antenatally growth-restricted singletons born at or near term to normotensive mothers. In growth-restricted singletons, a major birth defect was the dominant predictor, associated with a 30-fold increase in odds of CP. Identification of birth defects in the growth-restricted fetus or neonate may provide significant prognostic information.

Keywords: birth asphyxia; birth defects; pregnancy-induced hypertension; smoking; term and late preterm birth.