BackgroundFetal growth restriction (FGR) is associated with a suboptimal intrauterine environment, which may adversely impact fetal neurodevelopment. However, analysing neurodevelopmental outcomes by observed birthweight fails to differentiate between true FGR and constitutionally small infants and cannot account for iatrogenic intervention. This study aimed to determine the relationship between antenatal FGR and mid-childhood (age 5 to 7 years) educational outcomes. Methods and findingsThe Pregnancy Outcome Prediction Study (2008-2012) was a prospective birth cohort conducted in a single maternity hospital in Cambridge, United Kingdom. Clinicians were blinded to the antenatal diagnosis of FGR. FGR was defined as estimated fetal weight (EFW) <10th percentile at approximately 36 weeks of gestation, plus one or more indicators of placental dysfunction, including ultrasonic markers and maternal serum levels of placental biomarkers. A total of 2,754 children delivered at term were divided into 4 groups: FGR, appropriate-for-gestational age (AGA) with markers of placental dysfunction, healthy small-for-gestational age (SGA), and healthy AGA (referent). Educational outcomes (assessed at 5 to 7 years using UK national standards) were assessed with respect to FGR status using regression models adjusted for relevant covariates, including maternal, pregnancy, and socioeconomic factors.Compared to healthy AGA (N = 1,429), children with FGR (N = 250) were at higher risk of "below national standard" educational performance at 6 years (18% versus 11%; aOR 1.68; 95% CI 1.12 to 2.48, p = 0.01). By age 7, children with FGR were more likely to perform below standard in reading (21% versus 15%; aOR 1.46; 95% CI 0.99 to 2.13, p = 0.05), writing (28% versus 23%; aOR 1.46; 95% CI 1.02 to 2.07, p = 0.04), and mathematics (24% versus 16%; aOR 1.49; 95% CI 1.02 to 2.15, p = 0.03). This was consistent whether FGR was defined by ultrasound or biochemical markers. The educational attainment of healthy SGA children (N = 126) was comparable to healthy AGA, although this comparison may be underpowered. Our study design relied on linkage of routinely collected educational data according to nationally standardised metrics; this design allowed a high percentage of eligible participants to be included in the analysis (75%) but excludes those children educated outside of government-funded schools in the UK. Our focus on pragmatic and validated measures of educational attainment does not exclude more subtle effects of the intrauterine environment on specific aspects of neurodevelopment. ConclusionsCompared to children with normal fetal growth and no markers of placental dysfunction, FGR is associated with poorer educational attainment in mid-childhood. Author summary Why was this study done? Previous studies have reported poor neurodevelopmental outcomes as a long-term consequence of low birth weight.However, analysis on the basis of birth weight alone does not distinguish fetal growth restriction (FGR) from a healthy small phenotype. What did the researchers do and find? Prospectively collected and meticulously phenotyped antenatal data from 2,754 children was linked to nationally validated measures of educational outcomes in mid-childhood.Attending clinicians were blinded to the antenatal diagnosis of FGR to avoid bias in clinical management, e.g., iatrogenic early-term delivery.We found that children with antenatally diagnosed FGR had approximately 70% and approximately 50% greater risk of not attaining educational standards at ages 6 and 7 (in reading, writing, and mathematics), respectively. What do these findings mean? FGR is associated with poorer educational in mid-childhood, and this association cannot be explained by iatrogenic harm arising from earlier delivery at term.This finding has important implications for the clinical management of FGR diagnosed in late pregnancy.
